Next Article in Journal
Synthesis of 2,6-Diamino-Substituted Purine Derivatives and Evaluation of Cell Cycle Arrest in Breast and Colorectal Cancer Cells
Next Article in Special Issue
Targeting Difficult Protein-Protein Interactions with Plain and General Computational Approaches
Previous Article in Journal
Phenolic Compounds and Bioactivity of Cytisus villosus Pourr.
Previous Article in Special Issue
Truly Target-Focused Pharmacophore Modeling: A Novel Tool for Mapping Intermolecular Surfaces
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(8), 1995; https://doi.org/10.3390/molecules23081995

Role of Resultant Dipole Moment in Mechanical Dissociation of Biological Complexes

1
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
2
Battelle Center for Mathematical Medicine, Nationwide Children’s Hospital, Columbus, OH 43215, USA
3
Center for Perinatal Research, Research Institute at Nationwide Children’s Hospital, Columbus, OH 43215, USA
4
Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, USA
Deceased 12 August 2015.
*
Author to whom correspondence should be addressed.
Received: 29 May 2018 / Revised: 7 August 2018 / Accepted: 8 August 2018 / Published: 10 August 2018
(This article belongs to the Special Issue Molecular Modeling in Drug Design)
Full-Text   |   PDF [950 KB, uploaded 10 August 2018]   |  

Abstract

Protein-peptide interactions play essential roles in many cellular processes and their structural characterization is the major focus of current experimental and theoretical research. Two decades ago, it was proposed to employ the steered molecular dynamics (SMD) to assess the strength of protein-peptide interactions. The idea behind using SMD simulations is that the mechanical stability can be used as a promising and an efficient alternative to computationally highly demanding estimation of binding affinity. However, mechanical stability defined as a peak in force-extension profile depends on the choice of the pulling direction. Here we propose an uncommon choice of the pulling direction along resultant dipole moment (RDM) vector, which has not been explored in SMD simulations so far. Using explicit solvent all-atom MD simulations, we apply SMD technique to probe mechanical resistance of ligand-receptor system pulled along two different vectors. A novel pulling direction—when ligand unbinds along the RDM vector—results in stronger forces compared to commonly used ligand unbinding along center of masses vector. Our observation that RDM is one of the factors influencing the mechanical stability of protein-peptide complex can be used to improve the ranking of binding affinities by using mechanical stability as an effective scoring function. View Full-Text
Keywords: steered molecular dynamics; all-atom molecular dynamics simulation; resultant dipole moment; mechanical stability; protein-peptide interactions steered molecular dynamics; all-atom molecular dynamics simulation; resultant dipole moment; mechanical stability; protein-peptide interactions
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Kouza, M.; Banerji, A.; Kolinski, A.; Buhimschi, I.; Kloczkowski, A. Role of Resultant Dipole Moment in Mechanical Dissociation of Biological Complexes. Molecules 2018, 23, 1995.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top