Computer Simulations Study of Biomolecules in Non-Aqueous or Cosolvent/Water Mixture Solutions

Roccatano, Danilo

doi:10.2174/138920308785132686

Cited by 39 publications

(35 citation statements)

References 148 publications

(253 reference statements)

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“…Knowledge‐based potential functions are used in many different types of computational protein studies, including protein structure prediction,1–5 protein design,6–9 docking applications,10–13 and protein folding mechanism studies 14–17. Many atomistic potential functions18–20 and coarse‐grained potential functions21–24 have been developed.…”

Section: Introductionmentioning

confidence: 99%

Multibody coarse‐grained potentials for native structure recognition and quality assessment of protein models

et al. 2011

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Summary Multi-body potentials have been of much interest recently because they take into account three dimensional interactions related to residue packing and capture the cooperativity of these interactions in protein structures. Our goal was to combine long range multi-body potentials and short range potentials to improve recognition of native structure among misfolded decoys. We optimized the weights for four-body non-sequential, four-body sequential and short range potentials in order to obtain optimal model ranking results for threading and have compared these data against results obtained with other potentials. (Twenty six different coarse-grained potentials from the Potentials ‘R’Us web server have been used.) Our optimized multi-body potentials outperform all other contact potentials in the recognition of the native structure among decoys, both for models from homology template-based modeling and from template-free modeling in CASP8 decoy sets. We have compared the results obtained for this optimized coarse-grained potentials, where each residue is represented by a single point, with results obtained by using the DFIRE potential, which takes into account atomic level information of proteins. We found that for all proteins larger than 80 amino acids our optimized coarse-grained potentials yield results comparable to those obtained with the atomic DFIRE potential.

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Section: Introductionmentioning

confidence: 99%

Multibody coarse‐grained potentials for native structure recognition and quality assessment of protein models

et al. 2011

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“…Although DMSO, as chaotropic solvents, can induce denaturation by the depletion of the functional water layer surrounding the proteins (Roccatano, 2008), the concentrations used in P450 BM-3 experimental studies are too low to explain its inhibitions as a denaturation effect. Moreover, the unmodified activity of the WT enzyme up to 14 % (v/v) compared with strongly reduced one of the single mutant suggested that the residue Phe87 is playing a major role in preventing the DMSO inhibition.…”

Section: Studies On Solvent Effectsmentioning

confidence: 99%

Structure, dynamics, and function of the monooxygenase P450 BM-3: insights from computer simulations studies

Roccatano

2015

J. Phys.: Condens. Matter

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Abstract. The monooxygenase P450 BM-3 is a NADPH-dependent fatty acid hydroxylase enzyme isolated from soil bacterium Bacillus megaterium. As a pivotal member of cytochrome P450 superfamily, it has been intensely studied for the comprehension of structure-dynamics-function relationships in this class of enzymes. In addition, due to its peculiar properties, it is also a promising enzyme for biochemical and biomedical applications. However, despite the efforts, the full understanding of the enzyme structure and dynamics is not yet achieved. Computational studies, in particular molecular dynamics (MD) simulations, are given important contributes to this endeavor by providing new insights at atomic level on the correlations between structure, dynamics and function of the protein. This topical review will summarize computational studies based on MD simulations of the cytochrome P450 BM-3 and it will give an outlook on future directions. 2

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“…Infact such α-helical stability enhancing substances have been shown to inhibit amyloidogenic α→β transition in Aβ 42 peptide [43]. Roccatano presents an excellent review of various MD studies performed using different solvent systems and suggested that fluorinated alcohols like TFE promote secondary structure even in small proteins and peptides [44].…”

Section: Tfe Promotes α-Helical Conformations In Tfe/watermentioning

confidence: 99%

Environmental polarity induces conformational transitions in a helical peptide sequence from bacteriophage T4 lysozyme and its tandem duplicate: a molecular dynamics simulation study

Kaur

Sasidhar

2015

J Mol Model

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Our recent molecular dynamics (MD) simulation of an insertion/duplication mutant 'L20' of bacteriophage T4 lysozyme demonstrated a solvent induced α→β transition in a loosely held duplicate helical region, while α-helical conformation in the parent region was relatively stabilized by its tertiary interactions with the neighboring residues. The solution NMR of the parent helical sequence, sans its protein context, showed no inherent tendency to adopt a particular secondary structure in pure water but showed α-helical propensity in TFE/water and SDS micelles. In this study we investigate the conformational preference of the 'parent' and 'duplicate' sequences, sans the protein context, in pure water and an apolar TFE/water solution. Apolar TFE/water solution is a model for non-polar protein context. We performed MD simulations of the two peptides, in explicit water and 80% (v/v) TFE/water, using GROMOS 53a6 force field, at 300 K and 1 bar (under NPT conditions). We show that in TFE/water mixture, salt bridges are stabilized by apolar TFE molecules and main chain-main chain hydrogen bonds promote the α-helical conformation, particularly in the duplicate peptide. Solvent exposure, in pure water, resulted in an α→β transition to form a triple stranded β-sheet structure in the 'duplicate' sequence, with a rare psi-loop topology, while a mixture of turn/bend conformations were adopted by the 'parent' sequence. Thus the differences in conformational preference of the parent and duplicate sequence sans protein context, in pure water and TFE/water, implicate the importance of the environment polarity in dictating the peptide conformation. Mechanism of folding of the observed psi-loop in the duplicate sequence gives insights into folding of this rare β-sheet topology.

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Computer Simulations Study of Biomolecules in Non-Aqueous or Cosolvent/Water Mixture Solutions

Cited by 39 publications

References 148 publications

Multibody coarse‐grained potentials for native structure recognition and quality assessment of protein models

Multibody coarse‐grained potentials for native structure recognition and quality assessment of protein models

Structure, dynamics, and function of the monooxygenase P450 BM-3: insights from computer simulations studies

Environmental polarity induces conformational transitions in a helical peptide sequence from bacteriophage T4 lysozyme and its tandem duplicate: a molecular dynamics simulation study

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