Authors

Cong Liu

Type

Text

Type

Thesis

Advisor

DIll, Ken A. | Simmerling, Carlos | Green, David F. | .

Date

2016-12-01

Keywords

DOCK refinement, MELD | Chemistry

Department

Department of Chemistry

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/77038

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

In order to bridge the computational gap between DOCK and MD-based methods, a pipeline was designed to combine external information derived from DOCK with replica exchange molecular dynamics using MELD, an algorithm recently developed by our lab. Our goal was to predict the lowest free energy binding pose within the DOCK ensemble, therefore enabling us to refine DOCK results in cases where the correct structure is incorrectly scored. Our method was tested on 8 such ‘scoring failures’ found in the DOCK database SB2012. Three protocols of extracting structural information from DOCK ensembles were designed and tested. Crystal-like poses were correctly identified from the DOCK ensemble using all three protocols. In particular, the prediction within 3Å of the crystal pose using information derived from “Automatically cluster and choose based on KGS penalty function†protocol demonstrated the ability of this pipeline to refine DOCK results. | 59 pages

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