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Articles 1 - 7 of 7
Full-Text Articles in Amino Acids, Peptides, and Proteins
Structural Analysis And Activity Correlation Of Amphiphilic Cyclic Antimicrobial Peptides Derived From The [W4R4] Scaffold, Shaima Ahmed El-Mowafi, Anastasia G. Konshina, Eman H. M. Mohammed, Nikolay A. Krylov, Roman G. Efremov, Keykavous Parang
Structural Analysis And Activity Correlation Of Amphiphilic Cyclic Antimicrobial Peptides Derived From The [W4R4] Scaffold, Shaima Ahmed El-Mowafi, Anastasia G. Konshina, Eman H. M. Mohammed, Nikolay A. Krylov, Roman G. Efremov, Keykavous Parang
Pharmacy Faculty Articles and Research
In our ongoing quest to design effective antimicrobial peptides (AMPs), this study aimed to elucidate the mechanisms governing cyclic amphiphilic AMPs and their interactions with membranes. The objective was to discern the nature of these interactions and understand how peptide sequence and structure influence antimicrobial activity. We introduced modifications into the established cyclic AMP peptide, [W4R4], incorporating an extra aromatic hydrophobic residue (W), a positively charged residue (R), or the unique 2,5-diketopiperazine (DKP). This study systematically explored the structure–activity relationships (SARs) of a series of cyclic peptides derived from the [W4R4] scaffold, …
Comparative Analysis Of Conformational Dynamics And Systematic Characterization Of Cryptic Pockets In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb.1 Spike Complexes With The Ace2 Host Receptor: Confluence Of Binding And Structural Plasticity In Mediating Networks Of Conserved Allosteric Sites, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao, Gennady M. Verkhivker
Comparative Analysis Of Conformational Dynamics And Systematic Characterization Of Cryptic Pockets In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb.1 Spike Complexes With The Ace2 Host Receptor: Confluence Of Binding And Structural Plasticity In Mediating Networks Of Conserved Allosteric Sites, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
In the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full-length trimer complexes …
Exploring Conformational Landscapes And Cryptic Binding Pockets In Distinct Functional States Of The Sars-Cov-2 Omicron Ba.1 And Ba.2 Trimers: Mutation-Induced Modulation Of Protein Dynamics And Network-Guided Prediction Of Variant-Specific Allosteric Binding Sites, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Exploring Conformational Landscapes And Cryptic Binding Pockets In Distinct Functional States Of The Sars-Cov-2 Omicron Ba.1 And Ba.2 Trimers: Mutation-Induced Modulation Of Protein Dynamics And Network-Guided Prediction Of Variant-Specific Allosteric Binding Sites, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Mathematics, Physics, and Computer Science Faculty Articles and Research
A significant body of experimental structures of SARS-CoV-2 spike trimers for the BA.1 and BA.2 variants revealed a considerable plasticity of the spike protein and the emergence of druggable binding pockets. Understanding the interplay of conformational dynamics changes induced by the Omicron variants and the identification of cryptic dynamic binding pockets in the S protein is of paramount importance as exploring broad-spectrum antiviral agents to combat the emerging variants is imperative. In the current study, we explore conformational landscapes and characterize the universe of binding pockets in multiple open and closed functional spike states of the BA.1 and BA.2 Omicron …
Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Mathematics, Physics, and Computer Science Faculty Articles and Research
Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …
From Deep Mutational Mapping Of Allosteric Protein Landscapes To Deep Learning Of Allostery And Hidden Allosteric Sites: Zooming In On “Allosteric Intersection” Of Biochemical And Big Data Approaches, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao
From Deep Mutational Mapping Of Allosteric Protein Landscapes To Deep Learning Of Allostery And Hidden Allosteric Sites: Zooming In On “Allosteric Intersection” Of Biochemical And Big Data Approaches, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta, Sian Xiao, Peng Tao
Mathematics, Physics, and Computer Science Faculty Articles and Research
The recent advances in artificial intelligence (AI) and machine learning have driven the design of new expert systems and automated workflows that are able to model complex chemical and biological phenomena. In recent years, machine learning approaches have been developed and actively deployed to facilitate computational and experimental studies of protein dynamics and allosteric mechanisms. In this review, we discuss in detail new developments along two major directions of allosteric research through the lens of data-intensive biochemical approaches and AI-based computational methods. Despite considerable progress in applications of AI methods for protein structure and dynamics studies, the intersection between allosteric …
Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Coarse-Grained Molecular Simulations And Ensemble-Based Mutational Profiling Of Protein Stability In The Different Functional Forms Of The Sars-Cov-2 Spike Trimers: Balancing Stability And Adaptability In Ba.1, Ba.2 And Ba.2.75 Variants, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Mathematics, Physics, and Computer Science Faculty Articles and Research
Evolutionary and functional studies have suggested that the emergence of Omicron variants can be determined by multiple fitness tradeoffs including immune escape, binding affinity, conformational plasticity, protein stability, and allosteric modulation. In this study, we embarked on a systematic comparative analysis of the conformational dynamics, electrostatics, protein stability, and allostery in the different functional states of spike trimers for BA.1, BA.2, and BA.2.75 variants. Using efficient and accurate coarse-grained simulations and atomistic reconstruction of the ensembles, we examined the conformational dynamics of the spike trimers that agree with the recent functional studies, suggesting that BA.2.75 trimers are the most stable …
Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova
Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova
Bioelectrics Publications
The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …