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Open AccessArticle

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
*
Author to whom correspondence should be addressed.
Deceased 12 August 2015.
Molecules 2018, 23(8), 1995; https://doi.org/10.3390/molecules23081995
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)
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
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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. https://doi.org/10.3390/molecules23081995

AMA 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(8):1995. https://doi.org/10.3390/molecules23081995

Chicago/Turabian Style

Kouza, Maksim; Banerji, Anirban; Kolinski, Andrzej; Buhimschi, Irina; Kloczkowski, Andrzej. 2018. "Role of Resultant Dipole Moment in Mechanical Dissociation of Biological Complexes" Molecules 23, no. 8: 1995. https://doi.org/10.3390/molecules23081995

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