PMID- 34041265
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210624
IS  - 2296-889X (Print)
IS  - 2296-889X (Electronic)
IS  - 2296-889X (Linking)
VI  - 8
DP  - 2021
TI  - Molecular Mechanics Study of Flow and Surface Influence in Ligand-Protein 
      Association.
PG  - 659687
LID - 10.3389/fmolb.2021.659687 [doi]
LID - 659687
AB  - Ligand-protein association is the first and critical step for many biological and 
      chemical processes. This study investigated the molecular association processes 
      under different environments. In biology, cells have different compartments where 
      ligand-protein binding may occur on a membrane. In experiments involving 
      ligand-protein binding, such as the surface plasmon resonance and continuous flow 
      biosynthesis, a substrate flow and surface are required in experimental settings. 
      As compared with a simple binding condition, which includes only the ligand, 
      protein, and solvent, the association rate and processes may be affected by 
      additional ligand transporting forces and other intermolecular interactions 
      between the ligand and environmental objects. We evaluated these environmental 
      factors by using a ligand xk263 binding to HIV protease (HIVp) with atomistic 
      details. Using Brownian dynamics simulations, we modeled xk263 and HIVp 
      association time and probability when a system has xk263 diffusion flux and a 
      non-polar self-assembled monolayer surface. We also examined different protein 
      orientations and accessible surfaces for xk263. To allow xk263 to access to the 
      dimer interface of immobilized HIVp, we simulated the system by placing the 
      protein 20A above the surface because immobilizing HIVp on a surface prevented 
      xk263 from contacting with the interface. The non-specific interactions increased 
      the binding probability while the association time remained unchanged. When the 
      xk263 diffusion flux increased, the effective xk263 concentration around HIVp, 
      xk263-HIVp association time and binding probability decreased non-linearly 
      regardless of interacting with the self-assembled monolayer surface or not. The 
      work sheds light on the effects of the solvent flow and surface environment on 
      ligand-protein associations and provides a perspective on experimental design.
CI  - Copyright (c) 2021 Kaushik and Chang.
FAU - Kaushik, Shivansh
AU  - Kaushik S
AD  - Department of Chemistry, University of Chemistry, Riverside, CA, United States.
FAU - Chang, Chia-En A
AU  - Chang CA
AD  - Department of Chemistry, University of Chemistry, Riverside, CA, United States.
LA  - eng
GR  - R01 GM109045/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20210510
PL  - Switzerland
TA  - Front Mol Biosci
JT  - Frontiers in molecular biosciences
JID - 101653173
PMC - PMC8142692
OTO - NOTNLM
OT  - GeomBD
OT  - drug design
OT  - ligand-receptor binding
OT  - molecular modeling
OT  - molecular recognition
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/05/28 06:00
MHDA- 2021/05/28 06:01
PMCR- 2021/01/01
CRDT- 2021/05/27 06:50
PHST- 2021/01/28 00:00 [received]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/05/27 06:50 [entrez]
PHST- 2021/05/28 06:00 [pubmed]
PHST- 2021/05/28 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fmolb.2021.659687 [doi]
PST - epublish
SO  - Front Mol Biosci. 2021 May 10;8:659687. doi: 10.3389/fmolb.2021.659687. 
      eCollection 2021.