A molecular dynamics simulation study on the propensity of Asn-Gly-containing heptapeptides towards β-turn structures: Comparison with ab initio quantum mechanical calculations

Abstract

Both molecular mechanical and quantum mechanical calculations play an important role in describing the behavior and structure of molecules. In this work, we compare for the same peptide systems the results obtained from folding molecular dynamics simulations with previously reported results from quantum mechanical calculations. More specifically, three molecular dynamics simulations of 5 μs each in explicit water solvent were carried out for three Asn-Gly-containing heptapeptides, in order to study their folding and dynamics. Previous data, based on quantum mechanical calculations within the DFT framework have shown that these peptides adopt β-turn structures in aqueous solution, with type I’ β-turn being the most preferred motif. The results from our analyses indicate that at least for the given systems, force field and simulation protocol, the two methods diverge in their predictions. The possibility of a force field-dependent deficiency is examined as a possible source of the observed discrepancy.

Folding molecular dynamics simulation of T‐peptide, a HIV viral entry inhibitor: Structure, dynamics, and comparison with the experimental data

“…The system preparation process and the simulation protocol have been previously described in detail 6–12 . In summary, the procedure is as follows.…”

“…The system preparation process and the simulation protocol have been previously described in detail. [6][7][8][9][10][11][12] In summary, the procedure is as follows. The starting peptide structure in the fully extended state, along with the addition of missing hydrogen atoms and the solvationionization of the system, were all performed using the program LEAP from the AMBER tools distribution.…”

“…The simulation protocol, as previously described, [6][7][8][9][10][11][12] was the following: the system was first energy minimized for 2000 conjugate gradient steps and then the temperature was increased with a ΔT step of 20 K until the final desired temperature of 320 K over a period of 32 ps. Subsequently, the system was equilibrated for 10 ps under constant temperature and pressure (NpT conditions) until the volume equilibrated.…”

The Curious Case of A31P, a Topology-Switching Mutant of the Repressor of Primer Protein: A Molecular Dynamics Study of Its Folding and Misfolding

“…The first, and as demonstrated by Shaw and co-workers, is that this force field showed the closest agreement with the experimental chemical shifts and NOEs in the data set by Mao et al comprising 41 folded proteins and the most stable simulations in the data set of Huang et al, comprising 11 folded proteins. The second reason is that this force field not only is one of the best for the study of proteins in the folded state but to our knowledge and experience is also one of the best-performing force fields for folding simulations of peptides and small proteins. ,− The known issue with the too-compact unfolded states produced by this force field is mostly irrelevant for this study which is initiated with proteins in the folded state.…”

“…The second aspect of the simulations that must be discussed is the absence of an enhanced sampling method, like, for example, adaptive tempering (which we have used in most of the folding studies we have previously reported ,− ). The reason for our choice not to use such a method is more subtle: Most enhanced sampling methods are equivalent to modifying, directly or indirectly, the energy landscape of the respective systems.…”