Our research focuses on methods to increase the efficiency of the sampling of conformational space during molecular dynamics (MD) simulations. Such sampling is critical for many applications of MD, specifically including (but not limited to) the calculation of free energy differences due to chemical or conformational changes in a molecule as well as prediction of the three-dimensional structure of biological molecules. We have performed simulations to calculate the anomeric free energy differences for several carbohydrates using the standard methods available in the AMBER suite of programs. Currently, we are implementing the Locally Enhanced Sampling (LES) method in AMBER, and have repeated the calculations using LES, determining the relative benefits than can be obtained as well as the computational overhead. Additionally, we are investigating possible methods to improve the ability of MD simulations to predict the conformation of biological molecules in solution. Most such predictions are severely restricted by the limited conformational sampling that can occur during affordable simulations. we have therefore also implemented the LES method into the MD portion of AMBER, and we are currently running extensive tests to judge the performance. we are using LES both alone and in combination with Simulated Annealing (SA), comparing the results from simulations of protein loops to those obtained by conventional MD simulations. We use the Computer Graphics Laboratory for visualization of the results of our simulations.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001081-21
Application #
6280144
Study Section
Project Start
1998-07-01
Project End
1999-06-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
21
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kozak, John J; Gray, Harry B; Garza-López, Roberto A (2018) Relaxation of structural constraints during Amicyanin unfolding. J Inorg Biochem 179:135-145
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Chu, Shidong; Zhou, Guangyan; Gochin, Miriam (2017) Evaluation of ligand-based NMR screening methods to characterize small molecule binding to HIV-1 glycoprotein-41. Org Biomol Chem 15:5210-5219
Portioli, Corinne; Bovi, Michele; Benati, Donatella et al. (2017) Novel functionalization strategies of polymeric nanoparticles as carriers for brain medications. J Biomed Mater Res A 105:847-858
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Nguyen, Hai Dang; Yadav, Tribhuwan; Giri, Sumanprava et al. (2017) Functions of Replication Protein A as a Sensor of R Loops and a Regulator of RNaseH1. Mol Cell 65:832-847.e4
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Sato, Daisuke; Shannon, Thomas R; Bers, Donald M (2016) Sarcoplasmic Reticulum Structure and Functional Properties that Promote Long-Lasting Calcium Sparks. Biophys J 110:382-390
Towse, Clare-Louise; Rysavy, Steven J; Vulovic, Ivan M et al. (2016) New Dynamic Rotamer Libraries: Data-Driven Analysis of Side-Chain Conformational Propensities. Structure 24:187-199

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