TY - JOUR
T1 - Advances in molecular dynamics simulations and enhanced sampling methods for the study of protein systems
AU - Lazim, Raudah
AU - Suh, Donghyuk
AU - Choi, Sun
N1 - Funding Information:
Funding: This work was supported by Bio and Medical Technology Development Program (NRF-2019M3E5D4065251) funded by the Ministry of Science and ICT (MSIT) and the Ministry of Health and Welfare (MOHW) through the National Research Foundation of Korea (NRF), Medical Research Center (MRC) grant (No. 2018R1A5A2025286), and the Mid-career Researcher Program (NRF-2017R1A2B4010084). It was also supported by RP-Grant 2020 of Ewha Womans University.
Funding Information:
This work was supported by Bio and Medical Technology Development Program (NRF-2019M3E5D4065251) funded by the Ministry of Science and ICT (MSIT) and the Ministry of Health and Welfare (MOHW) through the National Research Foundation of Korea (NRF), Medical Research Center (MRC) grant (No. 2018R1A5A2025286), and the Mid-career Researcher Program (NRF-2017R1A2B4010084). It was also supported by RP-Grant 2020 of Ewha Womans University.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Molecular dynamics (MD) simulation is a rigorous theoretical tool that when used efficiently could provide reliable answers to questions pertaining to the structure-function relationship of proteins. Data collated from protein dynamics can be translated into useful statistics that can be exploited to sieve thermodynamics and kinetics crucial for the elucidation of mechanisms responsible for the modulation of biological processes such as protein-ligand binding and protein-protein association. Continuous modernization of simulation tools enables accurate prediction and characterization of the aforementioned mechanisms and these qualities are highly beneficial for the expedition of drug development when effectively applied to structure-based drug design (SBDD). In this review, current all-atom MD simulation methods, with focus on enhanced sampling techniques, utilized to examine protein structure, dynamics, and functions are discussed. This review will pivot around computer calculations of protein-ligand and protein-protein systems with applications to SBDD. In addition, we will also be highlighting limitations faced by current simulation tools as well as the improvements that have been made to ameliorate their efficiency.
AB - Molecular dynamics (MD) simulation is a rigorous theoretical tool that when used efficiently could provide reliable answers to questions pertaining to the structure-function relationship of proteins. Data collated from protein dynamics can be translated into useful statistics that can be exploited to sieve thermodynamics and kinetics crucial for the elucidation of mechanisms responsible for the modulation of biological processes such as protein-ligand binding and protein-protein association. Continuous modernization of simulation tools enables accurate prediction and characterization of the aforementioned mechanisms and these qualities are highly beneficial for the expedition of drug development when effectively applied to structure-based drug design (SBDD). In this review, current all-atom MD simulation methods, with focus on enhanced sampling techniques, utilized to examine protein structure, dynamics, and functions are discussed. This review will pivot around computer calculations of protein-ligand and protein-protein systems with applications to SBDD. In addition, we will also be highlighting limitations faced by current simulation tools as well as the improvements that have been made to ameliorate their efficiency.
KW - Binding free energy
KW - Enhanced sampling
KW - Molecular dynamics simulation
KW - Protein-ligand binding affinity
KW - Protein-protein interactions
UR - http://www.scopus.com/inward/record.url?scp=85090318190&partnerID=8YFLogxK
U2 - 10.3390/ijms21176339
DO - 10.3390/ijms21176339
M3 - Review article
C2 - 32882859
AN - SCOPUS:85090318190
SN - 1661-6596
VL - 21
SP - 1
EP - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 17
M1 - 6339
ER -