Determination of the Potential of Mean Force of Aromatic Amino Acid Complexes in Various Solvents Using Molecular Dynamics Simulations:  The Case of the Tryptophan−Histidine Pair

2001 ◽  
Vol 105 (32) ◽  
pp. 7835-7846 ◽  
Author(s):  
Francesco Luigi Gervasio ◽  
Riccardo Chelli ◽  
Massimo Marchi ◽  
Piero Procacci ◽  
Vincenzo Schettino
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Aromatic Amino Acid ◽  
Potential Of Mean Force ◽  
Amino Acid Complexes ◽  
Dynamics Simulations

scholarly journals New CHARMM force field parameters for dehydrated amino acid residues, the key to lantibiotic molecular dynamics simulations

RSC Advances ◽  
2014 ◽  
Vol 4 (89) ◽  
pp. 48621-48631 ◽  
Author(s):  
Eleanor R. Turpin ◽  
Sam Mulholland ◽  
Andrew M. Teale ◽  
Boyan B. Bonev ◽  
Jonathan D. Hirst
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Force Field ◽  
Molecular Dynamics Simulations ◽  
Amino Acid Residues ◽  
Charmm Force Field ◽  
Force Field Parameters ◽  
Dynamics Simulations

scholarly journals A Novel Quali-Quantitative Defect of VWF

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1032-1032
Author(s):  
Tom Van De Berg ◽  
Alice Todaro ◽  
Joyce van Beers ◽  
Kanin Wichapong ◽  
Floor Heubel-Moenen ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Genetic Analysis ◽  
Molecular Dynamics Simulations ◽  
Mrna Level ◽  
Bleeding Tendency ◽  
Unknown Significance ◽  
Dynamics Simulations ◽  
Von Willebrand

Abstract Background Von Willebrand Factor (VWF) is a multimeric protein largely involved in both primary and secondary hemostasis. The diagnosis and classification of von Willebrand Disease (VWD) patients can be challenging. In this poster we explore the genetic defects and their structural consequences in a VWD patient with a disproportionately high bleeding phenotype for her VWD severity. A 31-year old female, initially diagnosed with VWD type 1, presented herself with a bleeding tendency (ISTH-BAT 13) disproportionate to the severity of her VWD with antigen levels of 36%. Additional analysis showed decreased FVIII-binding at 28%. The combination of both quantitative and functional defects of VWF was an indication for further genetic analysis in order to better define the subtype of VWD. Aims Genetic and structural analysis of VWF in a patient with a disproportionally high bleeding phenotype with regard to a mild decrease in VWF antigen. Methods Routine laboratory analysis for VWD was performed. Genetic screening was performed by exome sequencing of hemostasis related genes. VWF mRNA analysis was carried out by RT-PCR and Sanger sequencing. The X-ray structure of furin in complex with a peptide-based inhibitor (PDB ID: 6YD7) was used as a template to construct furin-VWF (759HR(R760S)SKRS764) complex. The derived structures (furin in complex with WT/R760S-VWF) were subjected to molecular dynamics (MD) simulations (200ns) and binding free energy (BFE) calculations by using standard parameters and protocols implemented in AMBER20 program. Results Routine analysis showed PFA-ADP and PFA EPI >300 seconds, VWF:ACT of 37% with a VWF:AG of 36%. Collagen binding and FVIII-binding were 46% and 28% respectively. Genetic analysis of the VWF gene disclosed 2 heterozygous variants of unknown significance (VUS): c.2771 G>A (exon 21, p.Arg924Gln) has a 1-2.5% population prevalence and has been previously described in type 1 and 2N VWD. The other VUS (c.2278 C>A; exon 17) is a novel mutation predicting a major amino acid substitution (p.Arg760Ser) in the D2-domain of VWF. Sequencing of exons 17 and 21 in the patient's VWF mRNA revealed homozygosity for the mutated allele at both mutation sites, indicating that the two variants are in cis and that the 'normal' allele is not expressed at mRNA level. Molecular dynamics simulations of the novel c.2278 C>A mutation (Arg760Ser) predicts a markedly decreased binding of furin to its VWF binding site, possibly decreasing or preventing VWF pro-peptide cleavage. This in turn has been shown to lead to reduced FVIII-binding of VWF. Conclusion Genetic analysis shows one polymorphism (c.2771 G>A) and one variation of unknown significance (c.2278 C>A) in the patient's VWF-gene. The polymorphism is known to be of low pathogenicity. The c. 2278 C>A mutation was not known in any of the mutation databases and is a novel VWF mutation. Both mutations were shown to be present on the same allele. As the wild-type allele was not expressed on mRNA level, all of the patient's VWF protein includes both amino acid substitutions. Modeling and molecular dynamics simulations show a markedly decreased affinity of furin to its cleavage site on the VWF protein due to the Arg760Ser substitution, likely resulting in a persistent pro-peptide binding to the mature VWF protein. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

2018 ◽  
Vol 40 (5) ◽  
pp. 716-727 ◽  
Author(s):  
Kevin F. Morris ◽  
Eugene J. Billiot ◽  
Fereshteh H. Billiot ◽  
Jordan A. Ingle ◽  
Kevin B. Krause ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Chiral Recognition ◽  
Key Factors ◽  
Dynamics Simulations
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