Extensive evaluation of environment-specific force field for ordered and disordered proteins.
Xiaochen Cui1, Hao Liu1, Ashfaq Ur Rehman1
1State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Department of Bioinformatics and Biostatistics, National Experimental Teaching Center for Life Sciences and Biotechnology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China. haifengchen@sjtu.edu.cn.
Physical Chemistry Chemical Physics : PCCP
|May 25, 2021
Summary
A new force field, ESFF1, accurately models intrinsically disordered proteins (IDPs) by capturing diverse conformations. This computational tool complements experimental data, aiding in understanding IDP function and disease association.
Area of Science:
- Biochemistry and structural biology
- Computational biophysics
- Protein science
Background:
- Intrinsically disordered proteins (IDPs) lack fixed tertiary structures, complicating their study.
- IDPs are implicated in various human diseases.
- Experimental methods struggle to capture the full conformational diversity of IDPs.
Purpose of the Study:
- To evaluate the performance of the environment-specific precise force field (ESFF1) for modeling intrinsically disordered proteins (IDPs).
- To compare ESFF1 with the ff14SB force field in reproducing protein conformations.
- To assess the utility of ESFF1 in understanding the sequence-disorder-function relationship of IDPs.
Main Methods:
- Molecular dynamics simulations were employed to sample protein conformations.
- The ESFF1 force field was used to model three typical IDPs and thirteen folded proteins.
- Nuclear Magnetic Resonance (NMR) observables were used to validate simulation results against experimental data.
Main Results:
- ESFF1 demonstrated improved accuracy in reproducing NMR observables for IDPs compared to ff14SB.
- Simulations using ESFF1 yielded more diverse conformational ensembles for IDPs than ff14SB.
- Both force fields showed comparable performance for folded proteins.
Conclusions:
- ESFF1 is a valuable tool for accurately modeling the conformational dynamics of IDPs.
- This force field enhances our ability to study IDPs and their roles in disease.
- ESFF1 facilitates the exploration of the sequence-disorder-function paradigm in IDPs.
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