Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem

Abstract

The use of enhanced sampling molecular dynamics simulations to facilitate the folding of proteins is a relatively new approach which has quickly gained momentum in recent years. Accelerated molecular dynamics (aMD) can elucidate the dynamic path from the unfolded state to the near-native state, “flattened” by introducing a non-negative boost to the potential. Alamethicin F30/3 (Alm F30/3), chosen in this study, belongs to the class of peptaibols that are 7–20 residue long, non-ribosomally synthesized, amphipathic molecules that show interesting membrane perturbing activity. The recent studies undertaken on the Alm molecules and their transmembrane channels have been reviewed. Three consecutive simulations of ~900 ns each were carried out where N-terminal folding could be observed within the first 100 ns, while C-terminal folding could only be achieved almost after 800 ns. It took ~1 μs to attain the near-native conformation with stronger potential boost which may take several μs worth of classical MD to produce the same results. The Alm F30/3 hexamer channel was also simulated in an E. coli mimicking membrane under an external electric field that correlates with previous experiments. It can be concluded that aMD simulation techniques are suited to elucidate peptaibol structures and to understand their folding dynamics.

Gaussian accelerated molecular dynamics: Principles and applications

“…In this review, we will present the principles and the most recent applications of GaMD. Robust GaMD has been established for advanced simulation studies of a wide range of biomolecular systems, especially the protein-nucleic acid interactions [63][64][65] such as the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 gene-editing system, 66,67 protein-protein/peptide interactions, [68][69][70][71][72] protein-ligand binding, 55,56,[73][74][75][76] protein folding, 77 protein enzymes, 52,58,[78][79][80][81][82][83][84][85][86][87][88][89][90][91][92] membrane proteins (including GPCRs, 68,69,73,76,[93][94][95] ion channels, 53,96 and γ-secretase 97 ) and carbohydrates, [98][99][100]…”

A Novel Computer-Aid Nanotechnology Targeting to Combat Antibiotics Resistance with Superbugs against COVID-19 Pandemic

“…Then, the identification and employment of new molecules able to interfere with plasmid stability, alone or in combination with conjugation inhibitors (COINs), could lead to a substantial impulse in the battle against the spread of AMR [50] (described in Figure 7). Table 1 summarized the possibility of new molecules entity as antimicrobial peptide against AMR using computer aid structure database construction [51][52][53][54][55][56][57][58][59][60][61][62][63] (Figure 6,7) (Table 1,2).…”

Plant antimicrobial peptides: structures, functions, and applications

“…In general, AMPs are small molecule polypeptides synthesized by ribosomes, in which the production of the mature polypeptides involves cleavage from larger protein precursors and further post-translational modifications. In addition, some AMPs can be synthesized through non-ribosomal peptide synthetases (Mukherjee et al 2011 ; Tyagi et al 2019 ). Many AMPs exhibit a broad-spectrum antibiotic activity against pathogenic bacteria (gram-negative and gram-positive), fungi, enveloped viruses, and parasites (Havenga et al 2019 ; Marcocci et al 2020 ; Zahedifard et al 2020 ).…”