Physical Sciences and Mathematics Commons^™

Evidence Of Direct Interaction Between Cisplatin And The Caspase-Cleaved Prostate Apoptosis Response-4 Tumor Suppressor, Krishna K. Raut, Samjhana Pandey, Gyanendra Kharel, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Prostate apoptosis response-4 (Par-4) tumor suppressor protein has gained attention as a potential therapeutic target owing to its unique ability to selectively induce apoptosis in cancer cells, sensitize them to chemotherapy and radiotherapy, and mitigate drug resistance. It has recently been reported that Par-4 interacts synergistically with cisplatin, a widely used anticancer drug. However, the mechanistic details underlying this relationship remain elusive. In this investigation, we employed an array of biophysical techniques, including circular dichroism spectroscopy, dynamic light scattering, and UV–vis absorption spectroscopy, to characterize the interaction between the active caspase-cleaved Par-4 (cl-Par-4) fragment and cisplatin. Additionally, elemental analysis was …

Triphlapan: Predicting Hla Molecules Binding Peptides Based On Triple Coding Matrix And Transfer Learning, Meng Wang, Chuqi Lei, Jianxin Wang, Yaohang Li, Min Li

Computer Science Faculty Publications

Human leukocyte antigen (HLA) recognizes foreign threats and triggers immune responses by presenting peptides to T cells. Computationally modeling the binding patterns between peptide and HLA is very important for the development of tumor vaccines. However, it is still a big challenge to accurately predict HLA molecules binding peptides. In this paper, we develop a new model TripHLApan for predicting HLA molecules binding peptides by integrating triple coding matrix, BiGRU + Attention models, and transfer learning strategy. We have found the main interaction site regions between HLA molecules and peptides, as well as the correlation between HLA encoding and binding …

A Dynamical Model Of Binding In Visual Cortex During Incremental Grouping And Search, Daniel Schmid, Daniel A. Braun, Heiko Neumann

MODVIS Workshop

Binding of visual information is crucial for several perceptual tasks. To incrementally group an object, elements in a space-feature neighborhood need to be bound together starting from an attended location (Roelfsema, TICS, 2005). To perform visual search, candidate locations and cued features must be evaluated conjunctively to retrieve a target (Treisman&Gormican, Psychol Rev, 1988). Despite different requirements on binding, both tasks are solved by the same neural substrate. In a model of perceptual decision-making, we give a mechanistic explanation for how this can be achieved. The architecture consists of a visual cortex module and a higher-order thalamic module. While the …

The Effect Of Metalation On Antimicrobial Piscidins Imbedded In Normal And Oxidized Lipid Bilayers, Ana Dreab, Craig A. Bayse

Chemistry & Biochemistry Faculty Publications

Metalation of the N-terminal Amino Terminal Cu(II)- and Ni(II)-binding (ATCUN) motif may enhance the antimicrobial properties of piscidins. Molecular dynamics simulations of free and nickelated piscidins 1 and 3 (P1 and P3) were performed in 3 : 1 POPC/POPG and 2.6 : 1 : 0.4 POPC/POPG/aldo-PC bilayers (POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine: POPG, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol; aldo-PC, 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine) bilayer models. Nickel(II) binding decreases the conformation dynamics of the ATCUN motif and lowers the charge of the N-terminus to allow it to embed deeper in the bilayer without significantly changing the overall depth due to interactions of the charged half-helix …

Turning Ligands On Their Side: Computational Investigation Into The Binding Of N2o And N2 In Transition Metal Complexes, Cole Donald

Electronic Theses and Dissertations

Common greenhouse gas nitrous oxide (N₂O) is a thermodynamically potent and environmentally benign oxidant, making it a desirable target for metal center activation. Unfortunately, N₂O is a poor ligand for transition metals due to its weak sigma-donating and pi-accepting properties; as a result, few transition metal complexes capable of interacting with N₂O have been found. As the primary source of all nitrogen in organisms, abundant gas dinitrogen (N₂) is a crucially important tiny molecule and an essential part of daily existence. However, due to its inertness, it has limited practical uses in …

Exploring The Structure And Activity Of Metallo-Tetracyclines, Shahedul Islam

USF Tampa Graduate Theses and Dissertations

Copper as a key component of electron transport chain of eukaryotes is an essential transition metal ion. Copper homeostasis in mammals complex and tightly regulated. Its strong reactivity together with binding with biologically important chemicals can have important repercussions in human health and overall environment. Tetracycline as one of most abundantly used antibiotic of the world has become abundant in the environment as well. Herein in this dissertation we take the journey to explore the complexation of tetracycline with metals in the environment and the intricate interaction between copper and tetracycline by investigating their oxidative behavior once they are complexed. …

Mechanism For Selective Binding Of Aromatic Compounds On Oxygen-Rich Graphene Nanosheets Based On Molecule Size/Polarity Matching, Heyun Fu, Bingyu Wang, Dongqiang Zhu, Zhicheng Zhou, Shidong Bao, Xiaolei Qu, Yong Guo, Lan Ling, Shourong Zheng, Pu Duan, Jingdong Mao, Klaus Schmidt-Rohr, Shu Tao, Pedro J.J. Alvarez

Chemistry & Biochemistry Faculty Publications

Selective binding of organic compounds is the cornerstone of many important industrial and pharmaceutical applications. Here, we achieved highly selective binding of aromatic compounds in aqueous solution and gas phase by oxygen-enriched graphene oxide (GO) nanosheets via a previously unknown mechanism based on size matching and polarity matching. Oxygen-containing functional groups (predominately epoxies and hydroxyls) on the nongraphitized aliphatic carbons of the basal plane of GO formed highly polar regions that encompass graphitic regions slightly larger than the benzene ring. This facilitated size match–based interactions between small apolar compounds and the isolated aromatic region of GO, resulting in high binding …

Dissecting Monomer-Dimer Equilibrium Of An Rnase P Protein Provides Insight Into The Synergistic Flexibility Of 5’ Leader Pre-Trna Recognition, Danyun Zeng, Ainur Abzhanova, Benjamin P. Brown, Nicholas J. Reiter

Chemistry Faculty Research and Publications

Ribonuclease P (RNase P) is a universal RNA-protein endonuclease that catalyzes 5’ precursor-tRNA (ptRNA) processing. The RNase P RNA plays the catalytic role in ptRNA processing; however, the RNase P protein is required for catalysis in vivo and interacts with the 5’ leader sequence. A single P RNA and a P protein form the functional RNase P holoenzyme yet dimeric forms of bacterial RNase P can interact with non-tRNA substrates and influence bacterial cell growth. Oligomeric forms of the P protein can also occur in vitro and occlude the 5’ leader ptRNA binding interface, presenting a challenge in accurately defining …

Interaction Of Alpha-Crystallin With Phospholipid Membranes, Laxman Mainali, William J. O'Brien, Raju Timsina

Physics Faculty Publications and Presentations

Purpose/Aim: The amount of membrane-bound α-crystallin increases significantly with age and cataract formation, accompanied by a corresponding decline in the level of α-crystallin in the lens cytoplasm. The purpose of this research is to evaluate the binding affinity of α-crystallin to the phospholipid membranes as well as the physical properties of the membranes after α-crystallin binding.

Materials and Methods: The continuous wave and saturation recovery electron paramagnetic resonance (EPR) methods were used to obtain the information about the binding affinity and the physical properties of the membrane. In this approach, the cholesterol analogue spin label CSL was incorporated in the …

A Foundational Study Of A New Synthetic Method Of Metal Carbonyl Clusters, Miles Shaun Millard

Boise State University Theses and Dissertations

“Traditional” Metal Carbonyl Clusters (MCCs) contain a framework of multiple metal atoms bound together through formal metal-metal (M-M) bonds. Current methods of synthesis result in different cluster sizes and lack a method to control growth. This project proposes a new method of MCC synthesis to build larger structures utilizing secondary non-covalent interactions to develop “non-traditional” MCCs. The N,N’-diarylurea moiety is a strong hydrogen bond donor/acceptor that can induce self-assembly into larger secondary structures. The union of metal carbonyl and urea chemistry provides a potential method of “non-traditional” MCC synthesis. This proof of concept experiment will elucidate foundational information such …

Novel Spectroscopic Tools To Differentiate Drug-Dna Binding Interactions, Fadwa Dhafer Hamad

Masters Theses

DNA-drug interactions play a major role in therapeutics, diagnostics, forensics and imaging. Drugs bind to DNA in several ways based on the mode of interaction and they alter protein-DNA interactions or breaks/cleaves DNA that can lead to the cure of the disease. The major goal of the research carried out in this thesis is to develop novel optical spectroscopic tools that can differentiate Drug-DNA binding interactions mode whether its intercalation or minor-groove binding. To achieve this goal, we developed two-photon absorption (2PA) cross-section based technique to differentiate between Drug-DNA binding modes. The investigations were carried out on two drug molecules, …

Mutagenic And Spectroscopic Investigation Of Ph Dependent Cooa Dna Binding, Brian R. Weaver

Chemistry Honors Papers

The carbon monoxide (CO) sensing heme protein, CooA, is a transcription factor which exists in several bacteria that utilize CO as an energy source. CooA positively regulates the expression of coo genes in the presence of CO such that the corresponding proteins may metabolize CO. The present studies have yielded the unexpected result that Fe(III) CooA binds DNA tightly at pH < 7, deviating from all previously reported work which indicate that CooA DNA binding is initiated only when the exogenous CO effector reacts with the Fe(II) CooA heme. This observation suggests that the disruption of one or more salt bridges upon effector binding may be a critical feature of the normal CooA activation mechanism. To test this possibility, several protein variants that eliminated a selected salt bridge for the CooA homolog from Rhodospirillum rubrum were prepared via site-directed mutagenesis. Samples of these variant proteins, which were overexpressed in Escherichia coli, were then characterized by spectroscopic methods and functional assays to investigate the impact these mutations had on CooA heme coordination …

Ligand Binding Studies Of A Peptide Targeting Helix 69 Of 23s Rrna In Bacterial Ribosomes, Hyosuk Seo

Wayne State University Dissertations

In the development of finding a peptide targeting H69 of 23S rRNA in bacterial ribosomes, phage display was employed at pH 5.5, a buffer condition previously reported of H69 preferring a closed conformation. After sequencing, several peptides were chosen through sequence alignment, followed by preparation using solid-phase peptide synthesis. The peptides were characterized using MALDI-TOF and purified with HPLC. A truncated peptide TARHIY was selected from FID assay. Through binding studies using ESI-MS, SPR, BLItz, and NMR, the binding properties of the peptide to H69 were determined, such as binding affinity, stoichiometry, and interaction site. The peptide exhibited moderate binding …

Synthesis And Characterization Of Azo-Guanidine Based Alcoholic Media Naked Eye Dna Sensor, Ataf A. Altaf, Uzma Hashmat, Muhammad Yousaf, Bhajan Lal, Shafiq Ullah, Alvin A. Holder, Amin Badshah

Chemistry & Biochemistry Faculty Publications

DNA sensing always has an open meadow of curiosity for biotechnologists and other researchers. Recently, in this field, we have introduced an emerging class of molecules containing azo and guanidine functionalities. In this study, we have synthesized three new compounds (UA1, UA6 and UA7) for potential application in DNA sensing in alcoholic medium. The synthesized materials were characterized by elemental analysis, FTIR, UV-visible, ¹H NMR and ¹³C NMR spectroscopies. Their DNA sensing potential were investigated by UV-visible spectroscopy. The insight of interaction with DNA was further investigated by electrochemical (cyclic voltammetry) and hydrodynamic (viscosity) studies. …

The Study Of Nf-Κb Peptide Mimics And How Proteins Bind Dna, Allee M. Murray

Honors College Theses

The protein complex nuclear factor kappa B (NF-κB) is widely considered to be one of the most influential transcription factors when studying cellular functions. Peptide mimics of NF-κB aim to inhibit DNA binding in order to displace the natural transcription factor, therefore inhibiting transcription and translation. In theory, NF-κB is not the problem; the real problem lies in directing the synthesis and expression of harmful proteins. In conjunction with this, the project aims to study NF-κB and its structure and function to determine what criteria are important for the binding of DNA in order to design a peptide that comes …

Blind Prediction Of Host-Guest Binding Affinities: A New Sampl3 Challenge, Hari S. Muddana, C Daniel Varnado, Christopher W. Bielawski, Adam R. Urbach, Lyle Isaacs, Matthew T. Geballe, Michael K. Gilson

Adam R Urbach

The computational prediction of protein–ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands—i.e., host–guest systems—represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge for host–guest binding affinities, through the incorporation of 11 new host–guest complexes. Ten participating research groups addressed this challenge with a variety of approaches. Statistical assessment indicates that, although most methods performed well at predicting some …

Peptide Inhibitor Of Complement C1 (Pic1) Rapidly Inhibits Complement Activation After Intravascular Injection In Rats, Julia A. Sharp, Pamela S. Hair, Haree K. Pallera, Parvathi S. Kumar, Clifford T. Mauriello, Julius O. Nyalwidhe, Cody A. Phelps, Dalnam Park, Nicole M. Thielens, Stephen M. Pascal, Waldon Chen, Diane M. Duffy, Frank A. Lattanzio, Kenji M. Cunnion, Neel K. Krishna

Chemistry & Biochemistry Faculty Publications

The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in preclinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathways of complement and is referred to as Peptide Inhibitor of Complement C1 (PIC1). In this study, we determined that the lead PIC1 variant demonstrates a salt-dependent binding to C1q, the initiator molecule of the classical pathway. Additionally, this peptide bound to the lectin pathway initiator …

Sorption Of Cr(Iii) And Cr(Vi) To High And Low Pressure Synthetic Nano-Magnetite (Fe3o4)Particles, Jason Parsons, Jeffrey Hernandez, Christina M. Gonzalez, J. L. Gardea-Torresdey

Chemistry Faculty Publications and Presentations

The binding of Cr(III) and Cr(VI) to synthetic nano-magnetie particles synthesized under open vessel conditions and a microwave assisted hydrothermal synthesis techniques was investigated. Batch studies showed that the binding of both the Cr(III) and Cr(VI) bound to the nano-materials in a pH dependent manner. The Cr(III) maximized at binding at pH 4 and 100% binding. Similarly, the Cr(VI) ions showed a maximum binding of 100% at pH 4. The data from the time dependency studies showed for the most part the majority of the binding occurred within the first 5 minutes of contact with the nanomaterial and remained constant …

Sorption Of Cr(Iii) And Cr(Vi) To High And Low Pressure Synthetic Nano-Magnetite (Fe3o4)Particles, Jason Parsons, Jeffrey Hernandez, Christina M. Gonzalez, J. L. Gardea-Torresdey

Chemistry Faculty Publications and Presentations

The binding of Cr(III) and Cr(VI) to synthetic nano-magnetie particles synthesized under open vessel conditions and a microwave assisted hydrothermal synthesis techniques was investigated. Batch studies showed that the binding of both the Cr(III) and Cr(VI) bound to the nano-materials in a pH dependent manner. The Cr(III) maximized at binding at pH 4 and 100% binding. Similarly, the Cr(VI) ions showed a maximum binding of 100% at pH 4. The data from the time dependency studies showed for the most part the majority of the binding occurred within the first 5 minutes of contact with the nanomaterial and remained constant …

Romeo: A System For More Flexible Binding-Safe Programming, Paul Stansifer, Mitchell Wand

Mitchell Wand

Current languages for safely manipulating values with names only support term languages with simple binding syntax. As a result, no tools exist to safely manipulate code written in those languages for which name problems are the most challenging. We address this problem with Romeo, a language that respects α-equivalence on its values, and which has access to a rich specification language for binding, inspired by attribute grammars. Our work has the complex-binding support of David Herman's λm, but is a full-fledged binding-safe language like Pure FreshML.

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego F. Amado Torres

Diego Amado Torres

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Fluorescence Quenching Study Of Moxifloxacin Interaction With Calf Thymus Dna, Yunkai Lv, Pan Li, Miao-Lun Jiao, Bao-Sheng Liu, Chao Yang

Turkish Journal of Chemistry

Moxifloxacin (MOX) is a fourth-generation synthetic fluoroquinolone antibacterial agent with many important therapeutic properties. Fluorescence quenching was used to study the interaction of MOX with calf thymus DNA (ct-DNA) in aqueous solution. The intercalative binding mode and a static quenching mechanism were confirmed by the Stern--Volmer quenching rate constant (K_q) of 3.48 \times 10^{11} M^{-1} s^{-1} at 298 K. The thermodynamic parameters (\Delta H = --118.4 KJ mol^{-1} and \Delta S = --299.4 J mol^{-1} K^{-1}) were calculated at different temperatures, and they indicate that the main forces between MOX and ct-DNA are hydrogen bonding and Van der Waals force. …

Substrate Binding And Reduction Mechanism Of Molybdenum Nitrogenase, Zhiyong Yang

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

As a key constituent of proteins, nucleic acids, and other biomolecules, nitrogen is essential to all living organisms including human beings. Dinitrogen represents the largest pool of nitrogen, about 79% of the Earth’s atmosphere, yet it is unusable by most living organisms due to its inertness. There are two ways to fix this inert dinitrogen to usable ammonia. One is the industrial Haber-Bosch process, which needs to be conducted at high temperature and pressure. This process uses a lot of the non-renewable fossil fuel as the energy source. The other major pathway is the biological nitrogen fixation carried out by …

Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker

Professor Nick E Dixon

The flesh-eating bacterium group A Streptococcus (GAS) binds and activates human plasminogen, promoting invasive disease. Streptococcal surface enolase (SEN), a glycolytic pathway enzyme, is an identified plasminogen receptor of GAS. Here we used mass spectrometry (MS) to confirm that GAS SEN is octameric, thereby validating in silico modeling based on the crystal structure of S. pneumoniae -enolase. Site-directed mutagenesis of surface-located lysine residues (SENK252+255A, SENK304A, SENK334A, SENK344E, SENK435L and SEN434-435) was used to examine their roles in maintaining structural integrity, enzymatic function and plasminogen binding. Structural integrity of the GAS SEN octamer was retained for all mutants except SENK344E, as …

Helicase-Binding To Dnai Exposes A Cryptic Dna-Binding Site During Helicase Loading In Bacillus Subtilis, Charikleia Ioannou, Patrick M. Schaeffer, Nicholas E. Dixon, Panos Soultanas

Professor Nick E Dixon

The Bacillus subtilis DnaI, DnaB and DnaD proteins load the replicative ring helicase DnaC onto DNA during priming of DNA replication. Here we show that DnaI consists of a C-terminal domain (Cd) with ATPase and DNA-binding activities and an N-terminal domain (Nd) that interacts with the replicative ring helicase. A Zn21-binding module mediates the interaction with the helicase and C67, C70 and H84 are involved in the coordination of the Zn21. DnaI binds ATP and exhibits ATPase activity that is not stimulated by ssDNA, because the DNAbinding site on Cd is masked by Nd. The ATPase activity resides on the …

A Novel Zinc-Binding Fold In The Helicase Interaction Domain Of The Bacillus Subtilis Dnal Helicase Loader, Karin V. Loscha, Kristaps Jaudzems, Charikleia Ioannou, Xun-Cheng Su, Flynn R. Hill, Gottfried Otting, Nicholas E. Dixon, Edvards Liepinsh

Professor Nick E Dixon

The helicase loader protein DnaI (the Bacillus subtilis homologue of Escherichia coli DnaC) is required to load the hexameric helicase DnaC (the B. subtilis homologue of E. coli DnaB) onto DNA at the start of replication. While the C-terminal domain of DnaI belongs to the structurally well-characterized AAA+ family of ATPases, the structure of the N-terminal domain, DnaI-N, has no homology to a known structure. Three-dimensional structure determination by nuclear magnetic resonance (NMR) spectroscopy shows that DnaI presents a novel fold containing a structurally important zinc ion. Surface plasmon resonance experiments indicate that DnaI-N is largely responsible for binding of …

Binding Of The Molecular Chaperone Alphab-Crystallin To Abeta Amyloid Fibrils Inhibits Fibril Elongation, Sarah L. Shammas, Christopher A. Waudby, Shuyu Wang, Alexander K. Buell, Tuomas P. Knowles, Heath W. Ecroyd, Mark E. Welland, John A. Carver, Christopher M. Dobson, Sarah Meehan

Heath Ecroyd

The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ42 fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ42. Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect …

Nmr Spectroscopy Of 14-3-3zeta Reveals A Flexible C-Terminal Extension: Differentiation Of The Chaperone And Phosphoserine-Binding Activities Of 14-3-3zeta, H Fu, Danielle Williams, Heath Ecroyd, John Carver, Lixin Zhang, Huanqin Dai, Joanna Woodcock, K Goodwin

Heath Ecroyd

Intracellular 14-3-3 proteins bind to many proteins, via a specific phosphoserine motif, regulating diverse cellular tasks including cell signalling and disease progression. The 14-3-3 isoform is a molecular chaperone, preventing the stressinduced aggregation of target proteins in a manner comparable with that of the unrelated sHsps (small heat-shock proteins). 1H-NMR spectroscopy revealed the presence of a flexible and unstructured C-terminal extension, 12 amino acids in length, which protrudes from the domain core of 14-3-3 and is similar in structure and length to the C-terminal extension of mammalian sHsps. The extension stabilizes 14-3-3, but has no direct role in chaperone action. …

Defining The Structural Basis Of Human Plasminogen Binding By Streptococcal Surface Enolase, Amanda J. Cork, Slobodan Jergic, Sven Hammerschmidt, Bostjan Kobe, Vijay Pancholi, Justin L.P. Benesch, Carol V, Robinson, Nicholas E. Dixon, J Andrew Aquilina, Mark J. Walker

J. A. Aquilina

The flesh-eating bacterium group A Streptococcus (GAS) binds and activates human plasminogen, promoting invasive disease. Streptococcal surface enolase (SEN), a glycolytic pathway enzyme, is an identified plasminogen receptor of GAS. Here we used mass spectrometry (MS) to confirm that GAS SEN is octameric, thereby validating in silico modeling based on the crystal structure of S. pneumoniae -enolase. Site-directed mutagenesis of surface-located lysine residues (SENK252+255A, SENK304A, SENK334A, SENK344E, SENK435L and SEN434-435) was used to examine their roles in maintaining structural integrity, enzymatic function and plasminogen binding. Structural integrity of the GAS SEN octamer was retained for all mutants except SENK344E, as …

Blind Prediction Of Host-Guest Binding Affinities: A New Sampl3 Challenge, H. S. Muddana, C. D. Varnado, C. W. Bielawski, Adam R. Urbach, L. Isaacs, M. T. Geballe, M. K. Gilson

Chemistry Faculty Research

The computational prediction of protein–ligand binding affinities is of central interest in early-stage drug-discovery, and there is a widely recognized need for improved methods. Low molecular weight receptors and their ligands—i.e., host–guest systems—represent valuable test-beds for such affinity prediction methods, because their small size makes for fast calculations and relatively facile numerical convergence. The SAMPL3 community exercise included the first ever blind prediction challenge for host–guest binding affinities, through the incorporation of 11 new host–guest complexes. Ten participating research groups addressed this challenge with a variety of approaches. Statistical assessment indicates that, although most methods performed well at predicting some …