Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations

Abstract

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Graphical abstract Highlights The manuscript describes a computational study of the differential conformational behavior of the alanine dipeptide in diverse solvents including chloroform, methanol, DMSO, water and methyl formamide.  This study is important to understand the conformational behavior of peptides in diverse solvents, since the dialanine dipeptide is a model molecule to for peptides.  The manuscript discusses the role of inter-and intra-molecular interactions to understand the differential behavior of the molecule in the diverse solvents.2  This work aims to shed light into the controversy found in the literature between experimental and theoretical calculations of the dialanine dipeptide in water.  There has never been published a comparative computational study of the effect of the solvent on the molecule. AbstractIn general, peptides do not exhibit a well-defined conformational profile in solution. However, despite the experimental blurred picture associated with their structure, compelling spectroscopic evidence shows that peptides exhibit local order. The conformational profile of a peptide is the result of a balance between intramolecular interactions between different atoms of the molecule and intermolecular interactions between atoms of the molecule and the solvent. Accordingly, the conformational profile of a peptide will change upon the properties of the solvent it is soaked. To get insight into the balance between intra-and intermolecular interactions on the conformational preferences of the peptide backbone we have studied the conformational profile of the alanine dipeptide in diverse solvents using molecular dynamics as sampling technique. Solvents

Tripleurin XIIc: Peptide Folding Dynamics in Aqueous and Hydrophobic Environment Mimic Using Accelerated Molecular Dynamics

“…This observation can be attributed to the non-polar nature of chloroform environment. A recent study on the behavior of alanine dipeptide in explicit chloroform and water solvents by Rubio-Martinez et al [38] described that C 7 eq conformation only appears as a low energy minimum in chloroform. Standard residues like Ser2, Ala3, Gln6, Val9, Leu14, Val16, and Gln17 show energy minima strictly in the right-handed α-region.…”

Side-Chain Polarity Modulates the Intrinsic Conformational Landscape of Model Dipeptides

“…The conformational space can be segregated on the basis of Ramachandran angles (ϕ, ψ), following the convention described in the study of Perez and co-workers. 97 We find snapshots corresponding to all nine conformer families, for both the dipeptides, which suggests that our initial sampling based on MD is adequate, even if it was not exhaustive. As observed in earlier work, 97 some of the conformers are not true geometric minima on the gas-phase PEL and relax to other geometries upon minimization.…”

“… 97 We find snapshots corresponding to all nine conformer families, for both the dipeptides, which suggests that our initial sampling based on MD is adequate, even if it was not exhaustive. As observed in earlier work, 97 some of the conformers are not true geometric minima on the gas-phase PEL and relax to other geometries upon minimization. For Ac-Ala-NH 2 , there are only four potential energy minima, corresponding to the C 7 eq , C 5 , C 7 ax , and P II conformer families.…”

“…The conformers are labeled according to the Ramachandran angles (ϕ, ψ), following the convention described in the study of Perez and co-workers. 97 Bottom panel: Distinct low-energy conformers of the dipeptides. (a–d) The different conformers of Ac-Ala-NH 2 .…”

“…Some low-lying gas-phase structures may be destabilized substantially, and structures with relatively open Ramachandran angles may be favored as a result of solvent-mediated interactions. Various studies based on both ab initio ( 123 ) and molecular mechanics 97 methods predict that the C 7 eq conformation is not preferred in polar solvents, and the α R conformation emerges as the new global minimum. In line with these previous studies, we anticipate that the relative ordering of the free energy minima for both Ac-Ala-NH 2 and Ac-Ser-NH 2 will change in the solution-phase, although the global topographies of the landscapes are likely to be preserved.…”