Influence of Hydroxyproline On Mechanical Behavior of Collagen Mimetic Proteins Under Fraying Deformation - Molecular Dynamics Investigations

2021 ◽  
Author(s):  
Atul Rawal ◽  
Kristen Rhinehardt ◽  
Ram Mohan ◽  
Max Pendse
Keyword(s):  
Molecular Dynamics ◽  
Deformation Behavior ◽  
Mechanical Characteristics ◽  
Mechanical Deformation ◽  
Umbrella Sampling ◽  
Complete Separation ◽  
Binding Energies ◽  
Dynamics Modeling ◽  
Helical Protein ◽  
A Chain

Abstract Molecular dynamics modeling is used to simulate, model, and analyze mechanical deformation behavior and predictive properties of three different synthetic collagen proteins obtained from RSC-PDB, 1BKV, 3A08 & 2CUO, with varying concentrations of Hydroxyproline (HYP). Hydroxyproline is credited with providing structural support for the collagen protein molecules. Hydroxyproline's influence on these three synthetic collagen proteins' mechanical deformation behavior and predictive properties is investigated in the present paper. A detailed study and inference of the protein's mechanical characteristics associated with HYP content are investigated through fraying deformation behavior. A calculated Gibbs free energy value (?G) of each polypeptide a chain that corresponds with a complete unfolding of a single polypeptide a-chain from a triple-helical protein is obtained with umbrella sampling. The force needed for complete separation of the polypeptide a-chain from the triple-helical protein is analyzed for proteins to understand the influence of HYP concentration and are discussed in this paper. Along with a difference in ?G, different unfolding pathways for the molecule and individual chains are observed. The correlation between the fraying deformation mechanical characteristics and the collagen proteins' hydroxyproline content is provided in the present study via the three collagen proteins' resulting binding energies.

scholarly journals Study of Endogen Substrates, Drug Substrates and Inhibitors Binding Conformations on MRP4 and Its Variants by Molecular Docking and Molecular Dynamics

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1051
Author(s):  
Edgardo Becerra ◽  
Giovanny Aguilera-Durán ◽  
Laura Berumen ◽  
Antonio Romo-Mancillas ◽  
Guadalupe García-Alcocer
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Binding Energy ◽  
Binding Site ◽  
Binding Sites ◽  
Adenosine Monophosphate ◽  
Competitive Inhibitor ◽  
Umbrella Sampling ◽  
Coarse Grained ◽  
Nucleotide Polymorphisms

Multidrug resistance protein-4 (MRP4) belongs to the ABC transporter superfamily and promotes the transport of xenobiotics including drugs. A non-synonymous single nucleotide polymorphisms (nsSNPs) in the ABCC4 gene can promote changes in the structure and function of MRP4. In this work, the interaction of certain endogen substrates, drug substrates, and inhibitors with wild type-MRP4 (WT-MRP4) and its variants G187W and Y556C were studied to determine differences in the intermolecular interactions and affinity related to SNPs using protein threading modeling, molecular docking, all-atom, coarse grained, and umbrella sampling molecular dynamics simulations (AA-MDS and CG-MDS, respectively). The results showed that the three MRP4 structures had significantly different conformations at given sites, leading to differences in the docking scores (DS) and binding sites of three different groups of molecules. Folic acid (FA) had the highest variation in DS on G187W concerning WT-MRP4. WT-MRP4, G187W, Y556C, and FA had different conformations through 25 ns AA-MD. Umbrella sampling simulations indicated that the Y556C-FA complex was the most stable one with or without ATP. In Y556C, the cyclic adenosine monophosphate (cAMP) and ceefourin-1 binding sites are located out of the entrance of the inner cavity, which suggests that both cAMP and ceefourin-1 may not be transported. The binding site for cAMP and ceefourin-1 is quite similar and the affinity (binding energy) of ceefourin-1 to WT-MRP4, G187W, and Y556C is greater than the affinity of cAMP, which may suggest that ceefourin-1 works as a competitive inhibitor. In conclusion, the nsSNPs G187W and Y556C lead to changes in protein conformation, which modifies the ligand binding site, DS, and binding energy.

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