Paper Search Console

Home Search Page About Contact

Journal Title

Title of Journal: J Comput Aided Mol Des

Search In Journal Title:

Abbravation: Journal of Computer-Aided Molecular Design

Search In Journal Abbravation:

Publisher

Springer Netherlands

Search In Publisher:

DOI

10.1007/bf02737711

Search In DOI:

ISSN

1573-4951

Search In ISSN:
Search In Title Of Papers:

Dependency of ligand free energy landscapes on cha

Authors: Yuko Okamoto Toshimasa Tanaka Hironori Kokubo
Publish Date: 2010/05/22
Volume: 24, Issue: 8, Pages: 699-712
PDF Link

Abstract

We performed replicaexchange molecular dynamics REMD simulations of six ligands to examine the dependency of their free energy landscapes on charge parameters and solvent models Six different charge parameter sets for each ligand were first generated by RESP and AM1BCC methods using three different conformations independently RESP charges showed some conformational dependency On the other hand AM1BCC charges did not show conformational dependency and well reproduced the overall trend of RESP charges The free energy landscapes obtained from the REMD simulations of ligands in vacuum GeneralizedBorn GB and TIP3P solutions were then analyzed We found that even small charge differences can produce qualitatively different landscapes in vacuum condition but the differences tend to be much smaller under GB and TIP3P conditions The simulations in the GB model well reproduced the landscapes in the TIP3P model using only a fraction of the computational cost The proteinbound ligand conformations were rarely the global minimum states but similar conformations were found to exist in aqueous solution without proteins in regions close to the global minimum local minimum or intermediate statesWe are grateful for the insight discussions and collegiality provided by Dr Masaki Tomimoto The authors also thank Dr Douglas Cary for reading the manuscript The simulations and computations were performed on the TSUBAME Grid Cluster at Global Scientific Information and Computing Center of Tokyo Institute of Technology supported by the MEXT Open Advanced Research Facilities Initiative This work was supported in part by GrantsinAid for Scientific Research on Innovative Areas “Fluctuations and Biological Functions” and for the NextGeneration Super Computing Project Nanoscience Program from the Ministry of Education Culture Sports Science and Technology MEXT Japan

Keywords:

References

.
Search In Abstract Of Papers:
Other Papers In This Journal:
  1. Ligand design by a combinatorial approach based on modeling and experiment: application to HLA-DR4
  2. QSPR modeling of UV absorption intensities
  3. Reflections on the past 25 years
  4. Blowing a breath of fresh share on data
  5. Design and characterization of an engineered gp41 protein from human immunodeficiency virus-1 as a tool for drug discovery
  6. In memoriam Professor Corwin Hansch: birth pangs of QSAR before 1961
  7. Alignment-independent technique for 3D QSAR analysis
  8. Rapid discovery of inhibitors of Toxoplasma gondii using hybrid structure-based computational approach
  9. On the active site of mononuclear B1 metallo β-lactamases: a computational study
  10. Statistics in molecular modeling: a summary
  11. Design, synthesis and experimental validation of novel potential chemopreventive agents using random forest and support vector machine binary classifiers
  12. Active site acidic residues and structural analysis of modelled human aromatase: A potential drug target for breast cancer
  13. Conformational studies of immunodominant myelin basic protein 1–11 analogues using NMR and molecular modeling
  14. Evaluation of DOCK 6 as a pose generation and database enrichment tool
Search Result: