scholarly journals A Binary Matrix Method to Enumerate, Hierarchically Order and Structurally Classify Peptide Aggregation

2021 ◽  
Author(s):  
Amol Tagad ◽  
Reman Kumar Singh ◽  
G Naresh Patwari
Keyword(s):  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Radius Of Gyration ◽  
Peptide Aggregation ◽  
Two Dimensional ◽  
Centre Of Mass ◽  
Binary Matrix ◽  
Conventional Methods ◽  
Accessible Surface ◽  
Solvent Accessible Surface

Protein aggregation is a common and complex phenomenon in biological processes, yet a robust analysis of this aggregation process remains elusive. The commonly used methods such as centre-of-mass to centre-of-mass (COM-COM) distance, the radius of gyration (Rg), hydrogen bonding (HB) and solvent accessible surface area (SASA) do not quantify the aggregation accurately. Herein, a new and robust method that uses an aggregation matrix (AM) approach to investigate peptide aggregation in a MD simulation trajectory is presented. A nxn two-dimensional aggregation matrix (AM) is created by using the inter-peptide CA-CA cut-off distances which are binarily encoded (0 or 1). These aggregation matrices are analysed to enumerate, hierarchically order and structurally classify the aggregates. Moreover, the comparison between the present AM method and the conventional Rg, COM-COM and HB methods shows that the conventional methods grossly underestimate the aggregation propensity. Additionally, the conventional methods do not address the hierarchy and structural ordering of the aggregates, which the present AM method does. Finally, the present AM method utilises only nxn two-dimensional matrices to analyse aggregates consisting of several peptide units. To the best of our knowledge, this is a maiden approach to enumerate, hierarchically order and structurally classify peptide aggregation.

scholarly journals PAMAM dendrimer: a pH-controlled nanosponge

2017 ◽  
Vol 95 (9) ◽  
pp. 991-998 ◽  
Author(s):  
Prabal K. Maiti
Keyword(s):  
Accessible Surface Area ◽  
Pamam Dendrimer ◽  
Low Ph ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Water Molecules ◽  
Accessible Volume ◽  
Accessible Surface ◽  
Solvent Accessible Surface ◽  
Ph Controlled

Using fully atomistic molecular dynamics simulation that are several hundred nanoseconds long, we demonstrate the pH-controlled sponge action of PAMAM dendrimer. We show how at varying pH levels, the PAMAM dendrimer acts as a wet sponge; at neutral or low pH levels, the dendrimer expands noticeably and the interior of the dendrimer opens up to host several hundreds to thousands of water molecules depending on the generation number. Increasing the pH (i.e., going from low pH to high pH) leads to the collapse of the dendrimer size, thereby expelling the inner water, which mimics the ‘sponge’ action. As the dendrimer size swells up at a neutral pH or low pH due to the electrostatic repulsion between the primary and tertiary amines that are protonated at this pH, there is dramatic increase in the available solvent accessible surface area (SASA), as well as solvent accessible volume (SAV).

scholarly journals Mutations in RBD of SARS-CoV-2 Omicron variant result stronger binding to human ACE2 protein

2021 ◽  
Author(s):  
Cecylia Severin Lupala ◽  
Yongjin Ye ◽  
Hong Chen ◽  
Xiaodong Su ◽  
Haiguang Liu
Keyword(s):  
Complex Structure ◽  
Tight Binding ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Original Strain ◽  
Receptor Binding Domain ◽  
Bonding Interaction ◽  
Accessible Surface ◽  
Dynamics Simulations ◽  
Solvent Accessible Surface

The spreading of SARS-CoV-2 virus resulted the COVID-19 pandemic, which has caused more than 5 millions of death globally. Several major variants of SARS-CoV-2 have emerged and placed challenges in controlling the infections. The recently emerged Omicron variant raised serious concerns about reducing efficacy of antibodies or vaccines, due to its vast mutations. We modelled the complex structure of human ACE2 protein and the receptor binding domain of Omicron variant, then conducted atomistic molecular dynamics simulations to study the binding interactions. The analysis shows that the Omicron variant RBD binds more strongly to the human ACE2 protein than the original strain. The mutation at the ACE2-RBD interface enhanced the tight binding by increasing hydrogen bonding interaction and enlarging buried solvent accessible surface area.

scholarly journals Analysis of Two-State Folding Using Parabolic Approximation I: Hypothesis

2016 ◽  
Author(s):  
Robert S Sade
Keyword(s):  
Gibbs Energy ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Parabolic Approximation ◽  
Energy Functions ◽  
State Ensemble ◽  
The Mean ◽  
Accessible Surface ◽  
Transition State Ensemble ◽  
Solvent Accessible Surface

A model which treats the denatured and native conformers of spontaneously-folding fixed two-state systems as being confined to harmonic Gibbs energy-wells has been developed. Within the assumptions of this model the Gibbs energy functions of the denatured (DSE) and the native state (NSE) ensembles are described by parabolas, with the mean length of the reaction coordinate (RC) being given by the temperature-invariant denaturant m value. Consequently, the ensemble-averaged position of the transition state ensemble (TSE) along the RC, and the ensemble-averaged Gibbs energy of the TSE are determined by the intersection of the DSE and the NSE-parabolas. The equations derived enable equilibrium stability and the rate constants to be rationalized in terms of the mean and the variance of the Gaussian distribution of the solvent accessible surface area of the conformers in the DSE and the NSE. The implications of this model for protein folding are discussed.

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