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Articles 1 - 7 of 7
Full-Text Articles in Physical Sciences and Mathematics
Rational Design Of Small-Molecule Stabilizers Of Spermine Synthase Dimer By Virtual Screening And Free Energy-Based Approach, Zhe Zhang, Virginie Martiny, David Lagorce, Yoshihiko Ikeguchi, Emil Alexov, Maria A. Miteva
Rational Design Of Small-Molecule Stabilizers Of Spermine Synthase Dimer By Virtual Screening And Free Energy-Based Approach, Zhe Zhang, Virginie Martiny, David Lagorce, Yoshihiko Ikeguchi, Emil Alexov, Maria A. Miteva
Publications
Snyder-Robinson Syndrome (SRS) is a rare mental retardation disorder which is caused by the malfunctioning of an enzyme, the spermine synthase (SMS), which functions as a homo-dimer. The malfunctioning of SMS in SRS patients is associated with several identified missense mutations that occur away from the active site. This investigation deals with a particular SRS-causing mutation, the G56S mutation, which was shown computationally and experimentally to destabilize the SMS homo-dimer and thus to abolish SMS enzymatic activity. As a proof-of-concept, we explore the possibility to restore the enzymatic activity of the malfunctioning SMS mutant G56S by stabilizing the dimer through …
Problm Web Server: Protein And Membrane Placement And Orientation Package, Taylor Kimmett, Nicholas Smith, Shawn Witham, Marharyta Petukh, Subhra Sarkar, Emil Alexov
Problm Web Server: Protein And Membrane Placement And Orientation Package, Taylor Kimmett, Nicholas Smith, Shawn Witham, Marharyta Petukh, Subhra Sarkar, Emil Alexov
Publications
The 3D structures of membrane proteins are typically determined without the presence of a lipid bilayer. For the purpose of studying the role of membranes on the wild type characteristics of the corresponding protein, determining the position and orientation of transmembrane proteins within a membrane environment is highly desirable. Here we report a geometry-based approach to automatically insert a membrane protein with a known 3D structure into pregenerated lipid bilayer membranes with various dimensions and lipid compositions or into a pseudomembrane. The pseudomembrane is built using the Protein Nano-Object Integrator which generates a parallelepiped of user-specified dimensions made up of …
Computational And Experimental Approaches To Reveal The Effects Of Single Nucleotide Polymorphisms With Respect To Disease Diagnostics, Tugba G. Kucukkal, Ye Yang, Susan C. Chapman, Weiguo Cao, Emil Alexov
Computational And Experimental Approaches To Reveal The Effects Of Single Nucleotide Polymorphisms With Respect To Disease Diagnostics, Tugba G. Kucukkal, Ye Yang, Susan C. Chapman, Weiguo Cao, Emil Alexov
Publications
DNA mutations are the cause of many human diseases and they are the reason for natural differences among individuals by affecting the structure, function, interactions, and other properties of DNA and expressed proteins. The ability to predict whether a given mutation is disease-causing or harmless is of great importance for the early detection of patients with a high risk of developing a particular disease and would pave the way for personalized medicine and diagnostics. Here we review existing methods and techniques to study and predict the effects of DNA mutations from three different perspectives: in silico, in vitro and …
Chronic Beryllium Disease: Revealing The Role Of Beryllium Ion And Small Peptides Binding To Hla-Dp2, Marharyta Petukh, Bohua Wu, Shannon Stefl, Nick Smith, David Hyde-Volpe, Li Wang, Emil Alexov
Chronic Beryllium Disease: Revealing The Role Of Beryllium Ion And Small Peptides Binding To Hla-Dp2, Marharyta Petukh, Bohua Wu, Shannon Stefl, Nick Smith, David Hyde-Volpe, Li Wang, Emil Alexov
Publications
Chronic Beryllium (Be) Disease (CBD) is a granulomatous disorder that predominantly affects the lung. The CBD is caused by Be exposure of individuals carrying the HLA-DP2 protein of the major histocompatibility complex class II (MHCII). While the involvement of Be in the development of CBD is obvious and the binding site and the sequence of Be and peptide binding were recently experimentally revealed [1], the interplay between induced conformational changes and the changes of the peptide binding affinity in presence of Be were not investigated. Here we carry out in silico modeling and predict the Be binding to be within …
On The Modeling Of Polar Component Of Solvation Energy Using Smooth Gaussian-Based Dielectric Function, Lin Li, Chuan Li, Emil Alexov
On The Modeling Of Polar Component Of Solvation Energy Using Smooth Gaussian-Based Dielectric Function, Lin Li, Chuan Li, Emil Alexov
Publications
Traditional implicit methods for modeling electrostatics in biomolecules use a two-dielectric approach: a biomolecule is assigned low dielectric constant while the water phase is considered as a high dielectric constant medium. However, such an approach treats the biomolecule-water interface as a sharp dielectric border between two homogeneous dielectric media and does not account for inhomogeneous dielectric properties of the macromolecule as well. Recently we reported a new development, a smooth Gaussian-based dielectric function which treats the entire system, the solute and the water phase, as inhomogeneous dielectric medium (J Chem Theory Comput. 2013 Apr 9; 9(4): 2126-2136.). Here we examine …
On The Electrostatic Properties Of Homodimeric Proteins, Brandon Campbell, Marharyta Petukh, Emil Alexov, Chuan Li
On The Electrostatic Properties Of Homodimeric Proteins, Brandon Campbell, Marharyta Petukh, Emil Alexov, Chuan Li
Publications
A large fraction of proteins function as homodimers, but it is not always clear why the dimerization is important for functionality since frequently each monomer possesses a distinctive active site. Recent work (PLoS Computational Biology, 9(2), e1002924) indicates that homodimerization may be important for forming an electrostatic funnel in the spermine synthase homodimer which guides changed substrates toward the active centers. This prompted us to investigate the electrostatic properties of a large set of homodimeric proteins and resulted in an observation that in a vast majority of the cases the dimerization indeed results in specific electrostatic features, although not necessarily …
A Novel P.Leu(381)Phe Mutation In Presenilin 1 Is Associated With Very Early Onset And Unusually Fast Progressing Dementia As Well As Lysosomal Inclusions Typically Seen In Kufs Disease, Natalia Dolzhanskaya, Michael A. Gonzalez, Fiorella Sperziani, Shannon Stefl, Jeffrey Messing, Guang Y. Wen, Emil Alexov, S Stephan Zuchner, Milen Velinov
A Novel P.Leu(381)Phe Mutation In Presenilin 1 Is Associated With Very Early Onset And Unusually Fast Progressing Dementia As Well As Lysosomal Inclusions Typically Seen In Kufs Disease, Natalia Dolzhanskaya, Michael A. Gonzalez, Fiorella Sperziani, Shannon Stefl, Jeffrey Messing, Guang Y. Wen, Emil Alexov, S Stephan Zuchner, Milen Velinov
Publications
Whole exome sequencing in a family with suspected dominant Kufs disease identified a novel Presenilin 1 mutation p.Leu(381)Phe in three brothers who, along with their father, developed progressive dementia and motor deficits in their early 30s. All affected relatives had unusually rapid disease progression (on average 3.6 years from disease onset to death). In silico analysis of mutation p.Leu(381)Phe predicted more detrimental effects when compared to the common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of peripheral fibroblast cells of the proband showed lysosomal inclusions typical for Kufs disease. However his brain autopsy demonstrated typical changes of Alzheimer disease.