10/1/2015
Oasis, The Online Abstract Submission System
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Control/Tracking Number: 16A2858BPS Activity: Abstract Current Date/Time: 10/1/2015 3:47:04 PM PROTEIN SEQUENCE OPTIMIZATION WITH A POLARIZABLE FORCE FIELD: INSIGHTS FROM PDZ DOMAINS
Author Block: Jacob M. Litman1, Young Joo Sun1, Titus Hou1, Stephen D. LuCore2, Nicolas Panel3, Thomas Simonson3, Ernesto J. Fuentes1, Michael J. Schnieders1. 1Biochemistry Department, The University of Iowa, Iowa City, IA, USA, 2Biomedical Engineering Department, The University of Iowa, Iowa City, IA, USA, 3Laboratoire de Biochimie, Ecole
Polytechnique, Palaiseau, France. Abstract: Computational protein design (CPD) success is currently limited by a number of approximations, which often results in lists of candidate sequences with only a handful of genuine hits. Using a recent extension of the deadend elimination (DEE) algorithm to manybody potentials, we are able to complement pairwise CPD energy functions with the polarizable AMOEBA force field in a selfconsistent reaction field generalized Kirkwood continuum solvent. Results from energetic decompositions and preliminary sequence optimizations suggest solvent effects greatly dampen all but a handful of shortrange threeresidue interactions. Decompositions with a wildtype dielectric boundary only slightly reduce this damping, suggesting minimal impact of long range 3residue energies in implicit solvent models. In addition to these decompositions, we show preliminary sequence optimizations of PDZ domainligand complexes using both AMOEBA and OPLSAA force fields. Differences are observed for both sidechain rotamer preferences and for optimal amino acid sequence. These results pose a series of questions not just about fixedcharge, pairwise decomposable sequence design models, but also our novel polarizable, manybody optimization algorithms and how to use both approaches synergistically. : Author Disclosure Information: J.M. Litman: None. Y. Sun: None. T. Hou: None. S.D. LuCore: None. N. Panel: None. T. Simonson: None. E.J. Fuentes: None. M.J. Schnieders: None. Presentation Preference (Complete): : Platform or Poster If Yes, please provide the information below.: Yes Full Name: : Michael Schnieders Phone Number: : 6509953526 Email Address: : michael
[email protected] Sponsorship (Complete): * Are you a 2016 BPS Member?: Yes * Sponsor Full Name: : Michael Schnieders * Sponsor Email Address: : michael
[email protected] Topic (Complete): 1B Protein Structure, Prediction & Design ; 1A Protein Structure & Conformation Technique (Complete): First Selection: Molecular Modeling Second Selection: Molecular Dynamics Simulations Third Selection: Bioinformatics Fourth Selection: XRay Crystallography Payment (Complete): Your credit card order has been processed on Thursday 1 October 2015 at 3:30 PM. Status: Complete Biophysical Society 11400 Rockville Pike, Suite 800 Rockville, MD 20852 Phone: 2402905600 For technical inquiries, click here to contact OASIS Helpdesk or call 2173981792.
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10/1/2015
Oasis, The Online Abstract Submission System
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