Medicine and Health Sciences Commons^™

Sensory Modulation Disorder And Schizophrenia: Linking Behavioral Measures, Linda Olson

Theses and Dissertations

Schizophrenia is a devastating disorder affecting millions of people in the United States. Studies leading to new understanding of and intervention for this disorder are essential, as current interventions are minimally effective. The end result is high rates of re-hospitalization, impaired occupational performance and decreased community reintegration. According to the Diagnostic and Statistical Manual of Mental Disorders, symptoms of schizophrenia are categorized as positive or negative, with both types of symptoms impacting successful occupational engagement. Based on behavioral observations occupational therapists have hypothesized that this population may also experience sensory modulation disorder (SMD). Although electrophysiological studies support the presence of …

A Comparative Study Of Rotary Instrumentation Of The Maxillary First Premolar Buccal Root Utilizing Cone Beam Computed Tomography, Stephan Zigo

Theses and Dissertations

The study objective was to determine cementum-dentin wall thickness along the furcation groove in maxillary bifurcated first premolars after preparation with three successively larger, 0.04 tapered, nickel titanium rotary files. Pre-instrumentation and post-instrumentation imaging was accomplished utilizing Cone Beam Computed Tomography. All data was analyzed using an ANOVA. Instrumentation resulted in a significant reduction in dentin-cementum wall thickness (p < .001). At mid-groove, predicted dentin-cementum wall thickness (95% CI) was equal to or less than the proposed standard (0.50 mm) for apical file sizes 30, 35, and 40 respectively. Instrumentation of the mid-groove in maxillary first premolars reduces dentin-cementum wall thickness to levels that may be insufficient to ensure tooth integrity.

An In Vitro Comparison Of Cyclic Fatigue Of Profile® Vortex™ And Endosequence™ Rotary Nickel-Titanium Files, Fawaz Al-Foraih

Theses and Dissertations

The purpose of this study was to determine the number of rotations to fracture (cyclic fatigue) of the Profile® Vortex™ files (Dentsply Tulsa Dental Specialties, Tulsa, OK) compared to the EndoSequence™ files (Brasseler USA, Savannah, GA) using an in-vitro apparatus simulating a curved canal. Two hundred Profile® Vortex™ files of 25mm length were divided equally into ten groups, one for each of the Profile® Vortex™ files 20/0.04, 20/0.06, 25/0.04, 25/0.06, 30/0.04, 30/0.06, 35/0.04, 35/0.06, 40/0.04, and 40/0.06. Two hundred EndoSequence™ files of 25mm length were divided equally into ten groups of the same tip and taper sizes analogous to the …

Screening Prostate Specific Antigen Effects On Racial Disparate Mortality: A Propensity Score Analysis, R. David Mcnally

Theses and Dissertations

ABSTRACT SCREENING PROSTATE SPECIFIC ANTIGEN EFFECTS ON RACIAL DISPARATE MORTALITY: A PROPENSITY SCORE ANALYSIS By R. David McNally, Ph.D., M.S.H.A. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2011 Dissertation Chair: Jeffrey S. Legg, Ph.D., Associate Professor and Chair, Doctoral Program in Health Related Sciences Department of Radiation Sciences Prostate cancer is the most commonly diagnosed cancer among men in the United States. It is frequently cited that racial disparities in mortality between Caucasian and African American men with localized prostate cancer exist. In addition, …

The Relationship Of Physical Activity, Eating Behaviors, And Hunger Control To Weight Loss And Quality Of Life In Gastric Banding Patients, Nancy Baugh

Theses and Dissertations

Gastric banding as a weight loss surgery has increased in popularity in the United States since its approval by the Food and Drug Administration in 2001. Successful weight loss after weight loss surgery is most frequently defined as greater than 50 percent of excess weight loss (EWL). Systematic reviews show that the band is widely effective in achieving successful weight loss in most patients, however individual studies show more inconsistent outcomes. Although previous research supports gastric bypass surgery as having a positive effect on quality of life after gastric bypass, there is very little data to support this relationship in …

Anesthesia Recordkeeping: Accuracy Of Recall With Computerized And Manual Entry Recordkeeping, Thomas Corey Davis

Theses and Dissertations

ANESTHESIA RECORDKEEPING: ACCURACY OF RECALL WITH COMPUTERIZED AND MANUAL ENTRY RECORDKEEPING By Thomas Corey Davis, PhD A dissertation submitted in partial fulfillment of the requirements for the degree of PhD in Health Related Sciences at Virginia Commonwealth University. Virginia Commonwealth University, 2011 Major Director: Dr. Chuck Biddle Director of Research, Department of Nurse Anesthesia And Dr. Jeffery A. Green Assistant Chief of Anesthesiology, Department of Anesthesia Introduction: Anesthesia information management systems are rapidly gaining widespread acceptance. Aggressively promoted as an improvement to manual-entry recordkeeping systems in the areas of accuracy, quality improvement, billing and vigilance, these systems record all patient …

The Reliability And Validity Of A Simulated Airway Model That Quantifies Physical Forces Exerted During Endotracheal Intubation In A Clinically Demanding Scenario, Robert Matthews

Theses and Dissertations

The main purpose of this research was the development of an experimental model that allows for the assessment of pressure and thereby, the forces associated with interventions related to airway management. The foundation of this research was to develop, and assess the validity and reliability, of a method of quantifying the force experienced by a patient during airway management. Following IRB approval and the development of a unique simulation model that employs transducers situated in key anatomical locations to determine forces, a multivariate profile analysis with covariate of experience using a MANCOVA approach was conducted. The statistical design consisted of …

The Epidemiology Of Human Rabies Postexposure Prophylaxis In Virginia, 2002 And 2003, Marilyn Goss Haskell

Theses and Dissertations

Objective: To describe a sample that received human rabies postexposure prophylaxis (PEP) in Virginia as a result of animal exposures in 2002 and 2003 and to determine the extent to which PEP decisions were appropriate.Methods: PEP surveillance data were requested from 35 Virginia health districts within 5 regions. Retrospective chart review was used to gather demographic, exposure and source animal data from patient records and animal exposure reports. Descriptive statistics are presented. True exposures and appropriateness of PEP were defined using the 2004 Virginia Rabies Control Guidelines and the Recommendations of the 1999 Advisory Committee on Immunization Practices. The 2003 …

Identification And Characterization Of Low Ph-Triggered Conformational Changes In The Herpes Simplex Virus Glycoprotein B, Stephen Dollery

Theses and Dissertations

Herpesviruses can enter host cells by pH-dependent endocytic pathways in a cell-specific manner. The role of pH in herpesvirus endocytosis is unclear. Herpes simplex virus (HSV) is a paradigm for virus membrane fusion via a complex of glycoproteins. HSV glycoproteins B, D and the heterodimer H-L are necessary and sufficient for membrane fusion. This work analyzes the structure and function of HSV glycoproteins B, D, and H-L at neutral pH, and at the physiological low-pH encountered during endocytic entry. It is demonstrated that mildly acidic low pH triggers specific conformational changes in HSV gB at a pH of 5.7 to …

Evaluation Of A Training Intervention For Personal Care Assistants And The Effect Of Age And Extrinsic Job Satisfaction: Changes In Career Commitment And Job Satisfaction, Jason Rachel

Theses and Dissertations

Home care is a vital component of the United States healthcare delivery system. The demand for home care has steadily increased over the past decade and it is projected that this increase will continue over the next several decades. Moreover, the utilization of Medicaid waiver home and community-based care services has expanded to provide an alternative to the more costly institutional placement. In order to meet this growing demand while maintaining the cost-savings, the system relies primarily on the minimally trained, healthcare paraprofessionals known as Personal Care Assistants (PCAs). The present study examined the career commitment and job satisfaction of …

Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene Grin2a As A Parkinson's Disease Modifier Gene Via Interaction With Coffee, Taye H. Hamza, Honglei Chen, Erin M. Hill-Burns, Shannon L. Rhodes, Jennifer Montimurro, Denise M. Kay, Albert Tenesa, Victoria I. Kusel, Patricia Sheehan, Muthukrishnan Eaaswarkhanth, Dora Yearout, Ali Samii, John W. Roberts, Pinky Agarwal, Yvette Bordelon, Yikyung Park, Liyong Wang, Jianjun Gao, Jeffery M. Vance, Kenneth S. Kendler, Silviu-Alin Bacanu, William K. Scott, Beate Ritz, John Nutt, Stweart A. Factor, Cyrus P. Zabetian, Haydeh Payami

Psychiatry Publications

Our aim was to identify genes that influence the inverse association of coffee with the risk of developing Parkinson's disease (PD). We used genome-wide genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and we performed a genome-wide association and interaction study (GWAIS), testing each SNP's main-effect plus its interaction with coffee, adjusting for sex, age, and two principal components. We then stratified subjects as heavy or light coffee-drinkers and performed genome-wide association study (GWAS) in each group. We replicated the most significant SNP. Finally, we imputed the …

Acsl6 Is Associated With The Number Of Cigarettes Smoked And Its Expression Is Altered By Chronic Nicotine Exposure, Jingchun Chen, Darlene H. Brunzell, Kia J. Jackson, Andrew Van Der Vaart, Jennie Z. Ma, Thomas J. Payne, Richard Sherva, Lindsay A. Farrer, Pablo Gejman, Douglas F. Levinson, Peter Holmans, Steven H. Aggen, Imad Damaj, Po-Hsiu Kuo, Bradley T. Webb, Raymond Anton, Henry R. Kranzler, Joel Gelemter, Minf D. Li, Kenneth S. Kendler, Xiangning Chen

Psychiatry Publications

Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured …

Genomic Analysis Of Individual Differences In Ethanol Drinking: Evidence For Non-Genetic Factors In C57bl/6 Mice, Jennifer T. Wolstenholme, Jon A. Warner, Maria I. Capparuccini, Kellie J. Archer, Keith L. Shelton, Michael F. Miles

Pharmacology and Toxicology Publications

Genetic analysis of factors affecting risk to develop excessive ethanol drinking has been extensively studied in humans and animal models for over 20 years. However, little progress has been made in determining molecular mechanisms underlying environmental or non-genetic events contributing to variation in ethanol drinking. Here, we identify persistent and substantial variation in ethanol drinking behavior within an inbred mouse strain and utilize this model to identify gene networks influencing such “non-genetic” variation in ethanol intake. C57BL/6NCrl mice showed persistent inter-individual variation of ethanol intake in a two-bottle choice paradigm over a three-week period, ranging from less than 1 g/kg …

Influence Of Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodiafiltration On The Disposition Of Doripenem, Iolanda Cirillo, Nicole Vaccaro, Dainius Balis, Rebecca Redman, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The pharmacokinetics, safety, and tolerability of a single 1-hour, 500-mg intravenous infusion of doripenem were assessed in dialysis-dependent subjects with stage 5 chronic kidney disease undergoing continuous renal replacement therapy (CRRT) via 12-hour continuous venovenous hemofiltration (CVVH) (n = 6) or continuous venovenous hemodiafiltration (CVVHDF) (n = 5). Healthy volunteers were also assessed (n = 12). Concentrations of doripenem and the primary metabolite doripenem-M-1 were measured in plasma and ultrafiltrate or ultrafiltrate/dialysate by a validated liquid chromatography-tandem mass spectrometry method. In dialysis-dependent subjects, levels of systemic exposure to doripenem and doripenem-M-1 were approximately 3- and 5-fold greater, respectively, than those …

Applying An Empirical Hydropathic Forcefield In Refinement May Improve Low-Resolution Protein X-Ray Crystal Structures, Vishal N. Koparde, J. Neel Scarsdale, Glen E. Kellogg

Medicinal Chemistry Publications

Background

The quality of X-ray crystallographic models for biomacromolecules refined from data obtained at high-resolution is assured by the data itself. However, at low-resolution, >3.0 Å, additional information is supplied by a forcefield coupled with an associated refinement protocol. These resulting structures are often of lower quality and thus unsuitable for downstream activities like structure-based drug discovery.

Methodology

An X-ray crystallography refinement protocol that enhances standard methodology by incorporating energy terms from the HINT (Hydropathic INTeractions) empirical forcefield is described. This protocol was tested by refining synthetic low-resolution structural data derived from 25 diverse high-resolution structures, and referencing the resulting …

Ten Year Trends (1992 To 2002) In Sociodemographic Predictors And Indicators Of Alcohol Abuse And Dependence Among Whites, Blacks, And Hispanics In The U.S, Raul Caetano, Jonali Baruah, Karen G. Chartier

Social Work Publications

Background

The objective of this paper is to examine 10-year trends (1992–2002) in the number and type of indicators of DSM-IV abuse and dependence among Whites, Blacks and Hispanics in the U.S.

Methods

Data are from the 1991–1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES; n = 42,862) and the 2001–2002 National Epidemiologic Study on Alcohol and Related Conditions (NESARC; n = 43,093). Both surveys used multistage cluster sample procedures to select respondents 18 years of age and older from the U.S. household population.

Results

Increases in the prevalence of alcohol abuse between 1992 and 2002seem associated to a rise in …

Faculty Impressions Of Dental Students’ Performance With And Without Virtual Reality Simulation, Riki Gottlieb, Sharon K. Lanning, John C. Gunsolley, Judith A. Buchanan

Periodontics Publications

This study compared faculty perceptions and expectations of dental students’ abilities using virtual reality simulation (VRS) to those who did not use virtual reality simulation (non-VRS) in an operative dentistry preclinical course. A sixteen-item survey with a ten-point rating scale and three open-ended questions asked about students’ abilities in ergonomics, confidence level, performance, preparation, and self-assessment. The surveys were administered three times to a small group of preclinical faculty members. First, faculty members (n=12, 92 percent response rate) gave their perceptions of non-VRS students’ abilities at the end of their traditional course. Secondly, faculty members (n=13, 100 percent response rate) …

Genetic Analysis Of The Neurosteroid Deoxycorticosterone And Its Relation To Alcohol Phenotypes: Identification Of Qtls And Downstream Gene Regulation, Patrizia Porcu, Todd K. O'Buckley, Soomin C. Song, Jo Lynne Harenza, Lu Lu, Xusheng Wang, Michael F. Miles, A. Leslie Morrow

Neurology Publications

Background

Deoxycorticosterone (DOC) is an endogenous neurosteroid found in brain and serum, precursor of the GABAergic neuroactive steroid (3α,5α)-3,21-dihydroxypregnan-20-one (tetrahydrodeoxycorticosterone, THDOC) and the glucocorticoid corticosterone. These steroids are elevated following stress or ethanol administration, contribute to ethanol sensitivity, and their elevation is blunted in ethanol dependence.

Methodology/Principal Findings

To systematically define the genetic basis, regulation, and behavioral significance of DOC levels in plasma and cerebral cortex we examined such levels across 47 young adult males from C57BL/6J (B6)×DBA/2J (D2) (BXD) mouse strains for quantitative trait loci (QTL) and bioinformatics analyses of behavior and gene regulation. Mice were injected with saline …

Air Pollution & The Brain: Subchronic Diesel Exhaust Exposure Causes Neuroinflammation And Elevates Early Markers Of Neurodegenerative Disease, Shannon Levesque, Michael J. Surace, Jacob Mcdonald, Michelle L. Block

Anatomy and Neurobiology Publications

Background

Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood.

Objective

We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology.

Methods

Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months.

Results

DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception …

Chronic Apocynin Treatment Attenuates Beta Amyloid Plaque Size And Microglial Number In Happ(751)Sl Mice, Melinda E. Lull, Shannon Levesque, Michael J. Surace, Michelle L. Block

Anatomy and Neurobiology Publications

Background

NADPH oxidase is implicated in neurotoxic microglial activation and the progressive nature of Alzheimer's Disease (AD). Here, we test the ability of two NADPH oxidase inhibitors, apocynin and dextromethorphan (DM), to reduce learning deficits and neuropathology in transgenic mice overexpressing human amyloid precursor protein with the Swedish and London mutations (hAPP(751)SL).

Methods

Four month old hAPP(751)SL mice were treated daily with saline, 15 mg/kg DM, 7.5 mg/kg DM, or 10 mg/kg apocynin by gavage for four months.

Results

Only hAPP(751)SL mice treated with apocynin showed reduced plaque size and a reduction in the number of cortical microglia, when compared …

The Streptococcus Sanguinis Competence Regulon Is Not Required For Infective Endocarditis Virulence In A Rabbit Model, Jill E. Callahan, Cindy L. Munro, Todd Kitten

Philips Institute for Oral Health Research Publications

Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE orcomX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, …

Fto And Mc4r Gene Variants Are Associated With Obesity In Polycystic Ovary Syndrome, Kathryn G. Ewens, Michelle R. Jones, Wendy Ankener, Douglas R. Stewart, Margrit Urbanek, Andrea Dunaif, Richard S. Legro, Angela Chua, Ricardo Azziz, Richard S. Spielman, Mark O. Goodarzi, Jerome F. Strauss Iii

Obstetrics and Gynecology Publications

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility in women. It is also associated with metabolic disturbances that place women at increased risk for obesity and type 2 diabetes. There is strong evidence for familial clustering of PCOS and a genetic predisposition. However, the gene(s) responsible for the PCOS phenotypes have not been elucidated. This two-phase family-based and case-control genetic study was designed to address the question of whether SNPs identified as susceptibility loci for obesity in genome-wide association studies (GWAS) are also associated with PCOS and elevated BMI. Members of 439 families having at least one …

3d Mapping Of The Spry2 Domain Of Ryanodine Receptor 1 By Single-Particle Cryo-Em, Alex Peralvaerz-Marin, Hanshen Tae, Phillip G. Board, Marco G. Casarotto, Angela F. Dulhunty, Montserrat Samsó

Physiology and Biophysics Publications

The type 1 skeletal muscle ryanodine receptor (RyR1) is principally responsible for Ca2+release from the sarcoplasmic reticulum and for the subsequent muscle contraction. The RyR1 contains three SPRY domains. SPRY domains are generally known to mediate protein-protein interactions, however the location of the three SPRY domains in the 3D structure of the RyR1 is not known. Combining immunolabeling and single-particle cryo-electron microscopy we have mapped the SPRY2 domain (S1085-V1208) in the 3D structure of RyR1 using three different antibodies against the SPRY2 domain. Two obstacles for the image processing procedure; limited amount of data and signal dilution introduced by the …

State-Dependent Camp Binding To Functioning Hcn Channels Studied By Patch-Clamp Fluorometry, Shengjun Wu, Zhanna V. Vysotskaya, Xinping Xu, Changan Xie, Qinglian Liu, Lei Zhou

Physiology and Biophysics Publications

Abstract

One major goal of ion channel research is to delineate the molecular events from the detection of the stimuli to the movement of channel gates. For ligand-gated channels, it is challenging to separate ligand binding from channel gating. Here we studied the cyclic adenosine monophosphate (cAMP)-dependent gating in hyperpolarization-activated cAMP-regulated (HCN) channel by simultaneously recording channel opening and ligand binding, using the patch-clamp fluorometry technique with a unique fluorescent cAMP analog that fluoresces strongly in the hydrophobic binding pocket and exerts regulatory effects on HCN channels similar to those imposed by cAMP. Corresponding to voltage-dependent channel activation, we observed …

Cholesterol Sensitivity Of Kir2.1 Is Controlled By A Belt Of Residues Around The Cytosolic Pore, Avia Rosenhouse-Dantsker, Diomedes E. Logothetis, Irena Levitan

Physiology and Biophysics Publications

Abstract

Kir channels play an important role in setting the resting membrane potential and modulating membrane excitability. A common feature of several Kir channels is that they are regulated by cholesterol. Yet, the mechanism by which cholesterol affects channel function is unclear. We recently showed that the cholesterol sensitivity of Kir2 channels depends on several CD-loop residues. Here we show that this cytosolic loop is part of a regulatory site that also includes residues in the G-loop, the N-terminus, and the connecting segment between the C-terminus and the inner transmembrane helix. Together, these residues form a cytosolic belt that surrounds …

Challenges And Benefits Of Using A Virtual Community To Explore Nursing Concepts Among Baccalaureate Nursing Students, Linnea L. Carlson-Sabelli, Jean F. Giddens, Louis Fogg, Ruth A. Fiedler

School of Nursing Publications

This research study examines learner perceptions of benefits and challenges associated with the Neighborhood (NBH), an innovative pedagogy that fosters learner engagement and integration of nursing concepts using a “virtual community” as an alternative to lecture. First-semester students from five baccalaureate nursing programs that used the NBH intervention were divided into high (N = 78) and low faculty use (N = 203) groups. Qualitative analysis revealed that the NBH intervention promoted application of concepts to real life situation was engaging and “eye-opening,” allowing students to understand health care issues from a variety of perspectives. A major challenge was busy work …

Tryptophan Degradation In Women With Breast Cancer: A Pilot Study, Debra E. Lyon, Jeanne M. Walter, Angela R. Starkweather, Christine M. Schubert, Nancy L. Mccain

School of Nursing Publications

Background

Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy. …

Decreasing Mortality In Severe Sepsis And Septic Shock Patients By Implementing A Sepsis Bundle In A Hospital Setting, Sandra C. P. L. Shiramizo, Alexandre R. Marra, Marcelino S. Durao, Angela T. Paes, Michael B. Edmond, Oscar Fernando Pavao Dos Santos

Internal Medicine Publications

Background

The Surviving Sepsis Campaign (SSC) guidelines for the management of severe sepsis (SS) and septic shock (SSh) have been recommended to reduce morbidity and mortality.

Materials and Methods

A quasi-experimental study was conducted in a medical-surgical ICU. Multiple interventions to optimize SS and SSh shock patients' clinical outcomes were performed by applying sepsis bundles (6- and 24-hour) in May 2006. We compared bundle compliance and patient outcomes before (July 2005-April 2006) and after (May 2006-December 2009) implementation of the interventions.

Results

A total of 564 SS and SSh patients were identified. Prior to the intervention, compliance with the 6 …

The Living Textbook Project For Affordable Higher Education, Dayanjan S. Wijesinghe

Surgery Presentations

A blue print for ensuring that community college education remains affordable to the future generations via elimination of the cost of textbooks.

Bound Water At Protein-Protein Interfaces: Partners, Roles And Hydrophobic Bubbles As A Conserved Motif, Mostafa H. Ahmed, Francesca Spyrakis, Pietro Cozzini, Parijat K. Tripathi, Andrea Mozzarelli, J. Neel Scarsdale, Martin A. Safo, Glen E. Kellogg

Medicinal Chemistry Publications

Background

There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region.

Methodology

A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed …