Profile
Emil Alexov
Physics and Astronomy
Professor
864-656-3416
Kinard Lab 110 [Office]
Kinard Lab 215 [Office]
Educational Background
MS Physics, Plasma Physics, Sofia University, 1984
PhD Physics, Radiophysics, Sofia University, 1990
Profile/About Me
I am an interdisciplinary scientist, who believes in collaborative work and is always willing to explore new directions. I started my research career in plasma physics (Sofia University, Bulgaria), followed by research on protein crystals (Institute of Organic Chemistry, Bulgarian Academy of Sciences), and then working on bacteriorhodopsin as a visiting scientist in RIKEN (Japan). In 1995 I assumed postdoctoral position in City College of New York, and began computational work on bacterial photosynthesis and co-developed the Multi-Conformational Continuum Electrostatics (MCCE) algorithm to compute pKa’s of ionizable groups while allowing for sampling different side chain rotamers, water positions and orientations. In a series of works with our experimental collaborators, we revealed the key events involved in the coupled electron-proton transfer in the bacterial reaction center protein. In 2000 I joined the lab of Barry Honig at Columbia University as a senior scientist, where I worked on DelPhi, homology modeling of 3D protein structures and sequence alignment. There I co-developed a new version of DelPhi that allows for multiple dielectric constants in the Poisson-Boltzmann equation (PBE) numerical protocol, which explicitly calculates the energy of interaction between permanent charges and mobile ions in the water phase. In parallel, I was also interested in sequence alignment algorithms and co-developed a profile-to-profile sequence alignment tool (H-map) that takes advantage of structural information to deliver the sequence alignment via dynamic programming. In 2005, I assumed an independent position in Clemson University. During the first couple of years in Clemson University our work was focused on protein-protein interactions. My lab developed two protocols to predict the binding mode of two proteins: profile-to-profile (HOMBACOP) and structure-based (STRUBACOP) protocols. In parallel, following my previous independent works on pH-dependent phenomena, the lab produced a series of investigations on pH-optimum. We demonstrated that pH-optima of binding partners are the same, thus allowing the complex to be formed (and be stable) in the same subcellular organelle. We showed that the pH-optimum of stability and activity are correlated as well. Our new direction is developing methods, software and web servers to predict the effect of mutations on protein stability and protein-protein, protein-DNA/RNA binding. Furthermore, we use these methods along with third party approaches to study molecular effects originating from disease-causing mutations and thus to assess the pathogenicity of mutations see in human population.
I am also very active providing various services to scientific professional societies. I established and chaired the first Gordon Research Conference (GRC) “Human SNPs and disease” (2014) which is now a permanent program in the GRC list, running each second year. Furthermore, since 2012, I co-organized 8 symposia (one symposium per year) at the American Chemical Society annual meetings and a semester (4 workshops) on Emphasis Year on Mathematical Molecular Biosciences, Columbus, OH, sponsored by NSF. I am the Editor-in-Chief of the Journal of Computational Biophysics and Chemistry and currently I am a Guest Editor for several journals as PLOS Comp Biol, Genes, and IJMS. Over the years I had the privilege to serve on many NIH/NSF panels and funding agencies abroad. My commitment to the community is illustrated by numerous tools that we provide free of charge at http://compbio.clemson.edu and GitHub (list is too long).
From an educational standpoint, I am leading the effort of 35 Clemson faculty to establish a new MS/PhD program in “Medical Biophysics”. The uniqueness of this program is that it bridges academic and clinical research by linking the bio-oriented Clemson faculty with medical doctors at PRISMA Health (PRISMA Health is a conglomerate of hospitals here in SC). Last year I was awarded a sabbatical at PRISMA and initiated several collaborations with medical doctors there. The program is already approved by the board of trustees and we anticipate to be able to offer it in Fall 2021.
Research Interests
The research in the lab focuses on computational modeling of biological macromolecules and their assemblages as well as predicting biophysical quantities associated with them. One of the primary roles of the lab is to develop and maintain the popular software package DelPhi, which calculates electrostatic potentials and energies of systems comprised of biological macromolecules. We develop algorithms, software and web servers to predict the effects associated with human DNA mutations and then to identify small molecules (potential drugs) that can mitigate the disease-causing effects. We are very active in area of Personalized Medicine and Precision Diagnostics.
Research Group (Lab)
The research in the lab focuses on computational modeling of biological macromolecules and their assemblages as well as predicting biophysical quantities associated with them. One of the primary roles of the lab is to develop and maintain the popular software package DelPhi, which calculates electrostatic potentials and energies of systems comprised of biological macromolecules. We are also interested in modeling disease-causing missense mutations, pKa's of amino acids and nucleic groups, and pH-dependence of stability and binding. Visit our commercial site for details about services for human genetic differences and their interpretation.
Courses Taught
Courses Taught in Clemson University (Beginning Spring 2006)
PHYS 418, Modern Physics, S06
PHYS 311: Mathematical Methods for Theoretical Physics, F06, F07, F08
PHYS 417: Introduction to Biophysics, F06
PHYS 312: Mathematical Methods for Theoretical Physics, S07, S08, S09
PHYS 811: Mathematical Methods for Physicists, F10.
PHYS 812: Mathematical Methods for Physicists, S11.
PHYS 875: Computational Biophysics, F11.
PHYS 417: Intro to Biophysics, F12
PHYS 200: General Physics, S13
PHYS 875: Human DNA variants and diseases, F13
PHYS 819: Computational Biophysics, F14
PHYS 875: Human DNA variants and diseases, S15
PHYS 315: Introduction to computational physics, F15
PHYS 819: Human DNA variants and diseases, S16
PHYS 315: Introduction to computational physics, F16
PHYS 819: Computational Biophysics, S17
PHYS 315: Introduction to computational physics, F17
PHYS819: Computational Biophysics, S2018
PHYS 315: Introduction to computational physics, F18
Courses Taught in Bronx Community College, New York
Introductory Astronomy, each semester from 1997 until 2005. Lecture and labs.
Courses Taught in City College of New York
Classical Mechanics, Seminars, 1998-1999.
Courses Taught in Medical Academy, Bulgaria
Medical Physics, F1991, S1992.
Courses Taught in Sofia University, Bulgaria
Quantum Mechanics, F1990, S1991.
Courses Taught in Technical Institute, Bulgaria.
Engineering Physics, F1990.
Selected Publications
Li C, Jia Z, Chakravorty A, Pahari S, Peng Y, Basu S, Koirala M, Panday SK, Petukh M, Li L, Alexov E (2019). DelPhi Suite: New Developments and Review of Functionalities. J Comput Chem. Oct 30;40(28):2502-2508. doi: 10.1002/jcc.26006. PMID: 31237360.
Kucukkal TG, Petukh M, Li L, Alexov E. (2015). Structural and physico-chemical effects of disease and non-disease nsSNPs on proteins. Curr Opin Struct Biol. Jun;32:18-24. doi: 10.1016/j.sbi.2015.01.003. PMID: 25658850.
Peng Y, Alexov E. (2016). Investigating the linkage between disease-causing amino acid variants and their effect on protein stability and binding. Proteins. 84(2):232-9. doi: 10.1002/prot.24968. PMID: 26650512.
d. Li G, Pahari S, Krishna Murthy A, Liang S, Fragoza R, Yu H, Alexov E. (2020). SAAMBE-SEQ: A Sequence-based Method for Predicting Mutation Effect on Protein-protein Binding Affinity. Bioinformatics. Aug 31: btaa761. doi: 10.1093/bioinformatics/btaa761. Online ahead of print. PMID: 32866236
For more visit:
Research Group Website
Google Scholar
ResearchGate
Selected Talks
“Reproducing ensemble averaged quantities”: NSF-CBMS Conference: Mathematical Molecular Biosciences and Biophysics, May 13- 17, 2019. University of Alabama.
“Modeling the role of electrostatics in macromolecular recognition”: Oct. 3-5, 2019. seminar at University of Texas at El Paso.
“Super-Gaussian smooth dielectric for macromolecular modeling”: Tsinghua Sanya International Mathematics Forum (China) Dec 8-12, 2019.
“Disease-causing mutation in MePC2 protein affecting protein-DNA binding”, INSERM, France, April 2018.
“Physics-based approaches in molecular biology and their applications to reveal the mechanism of human diseases”, Auburn University, February 11, 2017.
“Multi-scale Modeling of Kinesin and Dynein Binding to Microtubules”, Yau Mathematical Sciences Center, China, December 22, 2016.
“Revealing molecular mechanism of mono genetic disorders and targeting disease-causing effects with small molecule binding”, Vanderbilt University, TN, April 22, 2016.
“Targeting disease-causing effects with small molecules binding”, MBI Emphasis Semester on Mathematical Molecular Biosciences, Dec. 6-11, 2015, MBI, Ohio, USA. https://mbi.osu.edu/video/player/?id=3772&title=Targeting+disease-causing+effects+with+small+molecules+binding
“Modeling Electrostatics in Biological Membranes and Membrane Proteins: Applications to Human Diseases”, MBI Emphasis Semester on Mathematical Molecular Biosciences, Nov. 18-24, 2015, MBI, Ohio, USA.
“Modeling Macromolecular Electrostatics with DelPhi Poisson-Boltzmann solver: Development and applications”, invited talk at Tianjin University, October 21, 2015, Beijing, China.
“Snyder-Robinson syndrome: molecular mechanism and rescuing the effect with small molecules”, Drug Discovery and Innovations, October 2-22, Beijing, China 2015.
“pKa calculations without defining molecular surface”, Protein electrostatics, July 8-12, 2015, Telluride, USA.
“Rett Syndrome Causing Mutations in MeCP2”, invited talk at University of Paris 7, April 28, 2015, Paris, France,
“Revealing molecular mechanism of Snyder-Robinson Syndrome and rescuing it with small molecule binding”, May 19, 2015, ORNL, USA.
“Listen to your genes”, May 8, 2015, TED talk. https://www.youtube.com/watch?v=BY7ZziM28UQ
“Electrostatics in Molecular Biology”, 2014 International Symposium on Laser and Computational Biophysics, June 15-17, Shanghai, China, 2014.
“Modeling Macromolecular Electrostatics with DelPhi Poisson-Boltzmann solver: Improvements and applications”, Oregon State University, October, 2014.
“Structure-based modeling of the effects of missense mutations associated with human disorders”, Genomics-2014, Raleigh, NC, September, 2014.
“Modeling Electrostatics in Molecular Biology via DelPhi Poisson-Boltzmann solver: Improvements and applications, NIH, April 7, 2014.
“Targeting diseases with small molecule rescuers”, NIH, May 8, 2014
Memberships
Member, American Physical Society (1990)
Member, American Chemical Society (2007)
Member, Biophysical Society (1995)
Member, Protein Society (1995)
Honors and Awards
2004 Science and Technology Agency Award (STA Fellowship), RIKEN, Japan.
2013 Outstanding Graduate Student Mentor, Clemson University, USA.
2014 Faculty Achievement in the Science, Clemson University, USA.
2018 Alumni Award for Outstanding Achievement in Research, Clemson, USA
2019 PRISMA Health sabbatical fellowship, USA
Links
Lab webpage
TED talk
Department web page
Clemson School of Health Research
Google Scholar
Journal of Computational Biophysics and Chemistry
