Physical Sciences and Mathematics Commons^™

Curling Of Flap Tips In Hiv-1 Protease As A Mechanism For Substrate Entry And Tolerance Of Drug Resistance, Walter Scott, Celia Schiffer

Celia A. Schiffer

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) protease is an essential viral protein that is a major drug target in the fight against Acquired Immune Deficiency Syndrome (AIDS). Access to the active site of this homodimeric enzyme is gained when two large flaps, one from each monomer, open. The flap movements are therefore central to the function of the enzyme, yet determining how these flaps move at an atomic level has not been experimentally possible.

RESULTS: In the present study, we observe the flaps of HIV-1 protease completely opening during a 10 ns solvated molecular dynamics simulation starting from …

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in …

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.

Ligand-Dependent Effects On The Conformational Equilibrium Of The Na+,K+-Atpase As Monitored By Voltage Clamp Fluorometry, Robert Dempski, Stefan Geys, Ernst Bamberg

Robert E. Dempski

Voltage clamp fluorometry was used to monitor conformational changes associated with electrogenic partial reactions of the Na(+),K(+)-ATPase after changes in the concentration of internal sodium (Na(+)(i)) or external potassium (K(+)(o)). To probe the effects of the Na(+)(i) concentration on the Na(+) branch of the Na(+),K(+)-ATPase, oocytes were depleted of Na(+)(i) and then loaded with external sodium (Na(+)(o)) using the amiloride-sensitive epithelial sodium channel. The K(+) branch of the Na(+),K(+)-ATPase was studied by exposing the oocytes to different K(+)(o) concentrations in the presence and absence of Na(+)(o) to obtain additional information on the apparent affinity for K(+)(o). Our results demonstrate that …

'Partial Derivatives: Are You Kidding?': Teaching Thermodynamics Using Virtual Substance, Chrystal Bruce, Carribeth Bliem, John Papanikolas

Chrystal D. Bruce

No abstract provided.

Physical And Structural Basis For The Strong Interactions Of The -Impy- Central Pairing Motif In The Polyamide F-Impyim, K. Buchmueller, S. Bailey, D. Matthews, Z. Taherbhai, J. Register, Z. Davis, Chrystal Bruce, C. O'Hare, J. Hartley, M. Lee

Chrystal D. Bruce

The polyamide f-ImPyIm has a higher affinity for its cognate DNA than either the parent analogue, distamycin A (10-fold), or the structural isomer, f-PyImIm (250-fold), has for its respective cognate DNA sequence. These findings have led to the formulation of a two-letter polyamide “language” in which the -ImPy- central pairings associate more strongly with Watson−Crick DNA than -PyPy-, -PyIm-, and -ImIm-. Herein, we further characterize f-ImPyIm and f-PyImIm, and we report thermodynamic and structural differences between -ImPy- (f-ImPyIm) and -PyIm- (f-PyImIm) central pairings. DNase I footprinting studies confirmed that f-ImPyIm is a stronger binder than distamycin A and f-PyImIm and …

Molecular Dynamics Simulations Of Sodium Dodecyl Sulfate Micelle In Water: The Behavior Of Water, Chrystal Bruce, Sanjib Senapati, Max Berkowitz, L. Perera, M. Forbes

Chrystal D. Bruce

Using a 5 ns explicit atom molecular dynamics simulation of a 60 monomer sodium dodecyl sulfate micellar system containing 7579 TIP3P water molecules, the behavior of water in different electrostatic environments was examined. Structural evaluation of the system revealed that penetration of water molecules into the micelle was restricted to the headgroup region, leaving a 12 Å water-free hydrocarbon core. Water molecules near the headgroup exhibit a distortion of the water−water hydrogen bonding network due to headgroup oxygen−water hydrogen bond formation. The dynamic implications of this distortion are manifested in the decay of the dipole autocorrelation function, Φ(t) and translational …

Molecular Dynamics Simulation Of Sodium Dodecyl Sulfate Micelle In Water: Micellar Structural Characteristics And Counterion Distribution, Chrystal Bruce, Max Berkowitz, Lalith Perera, Malcolm Forbes

Chrystal D. Bruce

An all-atom 5 nanosecond molecular dynamics simulation of a water-solvated micelle containing 60 sodium dodecyl sulfate monomers was performed. Structural properties such as the radius of gyration, eccentricity, micellar size, accessible surface area, dihedral angle distribution, carbon atom distribution, and the orientation of the monomers toward the micelle center of mass were evaluated. The results indicate a stable micellar system over the duration of the simulation. Evaluation of the structure and motion of the sodium counterions show (1) a long equilibration time (1 nanosecond) is required to achieve a stable distribution of counterions and (2) approximately 25% of the sodium …

Protein S-Thiolation And Dethiolation, James Thomas, Yuh-Cherng Chai, Che-Hun Jung

Yuh-Cherng Chai

No abstract provided.

Auger Analysis Of Si–H Bonding And Hydrogen Concentration In Hydrogenated Amorphous Silicon, Nancy Burnham, Aj Nelson, Ab Schwartzlander, Se Asher, Ll Kazmerski

Nancy A. Burnham

Auger electron spectroscopy line‐shape analysis of the Si‐L 2 3 V V peak has been performed on hydrogenated amorphous silicon (a‐Si:H). Both a‐Si:H produced by hydrogen implantation of siliconsingle crystals (for analytical standards) and thin films (fabricated for solar cell applications) were examined in these studies. Hydrogen concentrations were confirmed by secondary ion mass spectrometry, and samples having hydrogen content over the range 101 6–102 2 cm− 3 were evaluated. Correlations between the area under the deconvoluted L 2 3 V V transition peak and the known hydrogen content have resulted in a semiquantitative method of determining hydrogen concentration using …