The primary focus of research in our group is phase transitions that occur in protein solutions.
We are interested in the phase transitions because sometimes proteins in the human cells and tissues form condensed phases—crystals, aggregates, linear polymers, dense liquid droplets, and others—which almost always cause severe debilitating and deadly diseases: sickle cell anemia, eye cataract, Alzheimer’s and other neurological disorders, etc.
Our second set of motives is linked to the fact that the production of medications requires procedures that ensure narrow distributions of the micro-crystallites that comprise the drug preparation—this is a prerequisite for steady drug release. As more and more proteins are being tested for pharmaceutical applications, the need to control the nucleation and growth of protein micro-crystallites will increase.
A third group of factors that underlies our interests in this area is that phase transitions can be used to generate structures inaccessible to other methods—linear arrays of protein molecules, droplets of protein solutions that contain from 1,000 to 10,000 molecules and occupy atto-liter volumes, etc.
Traditionally, the formation of one particular ordered protein phase, the crystal, has been investigated to support the efforts of structural biologists in understanding the atomic structures of the protein molecules, and to shed light on the functions performed by these proteins.
Last but not least, we have argued that protein systems are particularly attractive models to elucidate the general mechanisms of phase transformations. The sizes of the protein molecules, from a few to several tens of nanometers and the characteristic timescales of the processes of growth of the new phases, of a few seconds and longer, are comparable to the lengthscales and time scales accessible to modern analytical techniques. This has allowed in-situ, real-time monitoring of the processes of phase transitions at the molecular scale.
In the logical framework of our research efforts, the first building block is the study of the interactions between the protein molecules in solution. Typically, such investigations are carried out in dilute solutions, relatively far from the phase diagram area of multiple phases, yet they have proven to be useful for a fuller insight into the phase transformations. We use static and dynamic light scattering techniques in house, and, in collaborations with colleagues, small angle x-ray scattering, to determine the second virial coefficient under varying external conditions, and from these data to deduce the potentials of interaction between the molecules. An additional gain from these data is that the second virial coefficient data allow evaluation of the solution non-ideality, and in this way a more accurate definition of the driving forces of the phase transformations.
A second group of efforts aims at determinations of phase diagrams of solutions of different proteins, i.e., on the thermodynamics of phase transformations. Depending on the phase line to be determined, we use microscopy and light scattering techniques.
As far as the kinetics of phase transitions is concerned, we investigate both the kinetics of generation of the new phase via nucleation or spinodal decomposition, and the processes of growth of the new phases.
We have three nucleation projects: we investigate the nucleation of dense liquid droplets of the protein lysozyme and hemoglobin, and its transition into spinodal decomposition as the supersaturation is increased; we investigate the nucleation of the polymer fibers of the sickle cell hemoglobin that underlie the deadly sickle cell anemia, and we investigate the nucleation of protein crystals.
In the area of new phase growth, we investigate the growth processes occurring at molecular, capillary, transport, and macroscopic lengthscales. These include incorporation of molecules into the respective growth sites, generation of growth sites and new layers, in the cases of crystal growth, supply of material to the growth sites by means of solute diffusion, interactions between the growth steps, step bunching and mean to control this phenomenon, defect generation and evolution, etc. We employ scanning probe and interferometry techniques that allow us to cover the various length- and time-scales involved.
- Protein Crystallization
- Physico-chemical aspects of sickle-cell anemia
- Nucleation and phase transitions in protein solutions
- Protein intermolecular interactions and phase diagrams
- Crystallization of membrane proteins
- Kinetics and Stability of Crystal Growth
- 3-D molecular graphics software
- Dr. Oleg Galkin: nucleation and dynamics of formation of protein solid phases
- Weichun Pan: interactions in solutions of proteins
- Yasser Qutub: crystallization of membrane proteins
- Luis Filobelo: nucleation of insulin crystals
- Panagiotis Katsonis: Monte Carlo simulations of phase diagrams
- Dimitra Georgiou: AFM characterization of protein crystals
- Mrinal Shah: pattern formation during phase transitions in protein solutions
April, 2003 — Dr. Vekilov's Research Group
From left: Yasser, Oleg, Panos, Mrinal, Ilya, Olga, Peter, Nick, Dimitra, Luis and Weichun
American Association for Crystal Growth Award, 2021
1000 Reasons to be Proud to be Bulgarian, Sofia, Bulgaria, 2021
Cullen College of Engineering Faculty Excellence Award, 2021
UH Excellence in Research, Scholarship, and Creative Achievement Award, 2019
Francqui International Professorship, Francqui Foundation, Belgium, 2014
John and Rebecca Moores Professorship, University of Houston, 2013
Senior Faculty Research Award, Cullen College of Engineering, University of Houston, 2013
Fellow, American Physical Society, Division of Biological Physics, 2010
UH Excellence in Research and Scholarship Award, 2006
DuPont Research Award, DuPont Chemical Company, 2002
UAH Foundation Research and Creative Achievement Award, 2001
International Union of Crystallography Young Scientist Award, Sixth International Conference on Crystallization of Biological Macromolecules, Hiroshima, Japan, 1995
Research Award by the International Human Frontiers Science Program, 1993 (declined)
Research Award by the Science and Technology Agency, Government of Japan, 1992
First Prize, Annual Research Session, Institute of Crystallography, Russian Acad. Sci., 1990
Shubnikov Prize of the Russian Academy of Sciences, 1986
Valedictorian (Otlichnik vypuska), School of Chemistry, M.V. Lomonosov Moscow University, 1985
Gold Medal, Ministry of Higher Education of the USSR, 1984
Diploma, Twelfth International Chemical Olympiad, Linz, Austria, 1980
- D. S. Yang, A. Saeedi, A. Davtyan, M. Fathi, M.B. Sherman, M. S. Safari, A. Klindziuk, M. C. Barton, N. Varadarajan, A. B. Kolomeisky, P.G.Vekilov, Mesoscopic Protein-rich Clusters Host the Nucleation of Mutant p53 Amyloid Fibrils. Proceedings of the National Academy of Sciences of the USA 118, e2015618118, 2021
- M. Kaissaratos, L. Filobelo, P.G. Vekilov, Two-step crystal nucleation is selected because of lower surface free energy barrier. Crystal Growth and Design 21, 5394-5402, 2021
- W. Ma, V. Balta, R. West, K.N. Newlin, O.Š. Miljanić, D.J. Sullivan, P.G. Vekilov, J.D. Rimer, A Second Mechanism Employed by Artemisinins to Suppress Plasmodium Falciparum Hinges on Inhibition of Hematin Crystallization. J. Biol. Chem. 296, 100123, 2021
- Y. Xu, K. Knapp, K.N. Le, N.P. Schafer, M.S. Safari, A. Davtyan, P.G. Wolynes, P.G. Vekilov, Multiple Frustrated Monomers at the Fibril Tip Constitute the Activated Complex for Amyloid b Fibril Growth. Proceedings of the National Academy of Sciences of the USA 118, e2110995118, 2021
- M. Warzecha, L. Verma, B.F.Johnston, J.C. Palmer, A.J. Florence, P.G. Vekilov, Olanzapine crystal symmetry originates in preformed centrosymmetric solute dimers. Nature Chemistry 12, 914-920, 2020
- P.G. Vekilov, Non-classical nucleation, in Crystallization via Non-Classical Pathways. Volume 1: Nucleation, Assembly, Observation & Application, Edited by Xin Zhang (ACS Books, Washington, DC) pp. 19-42, 2020
- R. Chakrabarti and P.G. Vekilov, Attraction between Permanent Dipoles and London Dispersion Forces Dominate the Thermodynamics of Organic Crystallization. Crystal Growth and Design 20, 7429-7438, 2020
- W. Ma, J.F. Lutsko, J.D. Rimer, P.G. Vekilov, Antagonistic cooperativity between crystallization modifiers. Nature 577, 497-501, 2020
- L. Lu, Z. Li, H. Li, X. Li, P.G. Vekilov, G.E. Karniadakis, Quantitative prediction of erythrocyte sickling for anti-polymerization activities in sickle cell disease. Science Advances 5, eaax3905., 2019
- M.S. Safari, Z. Wang, K. Tailor, A.B. Kolomeisky, J.C. Conrad, P.G. Vekilov, Anomalous dense liquid condensates host the nucleation of tumor suppressor p53 fibrils. iScience 12, 342-355., 2019
- K.N. Olafson, J.D. Rimer, P.G. Vekilov, Early onset of kinetic roughening due to finite step width in hematin crystallization. Phys. Rev. Lett. 119, 198101, 2017
- K.N. Olafson, T.Q. Nguyen, J.D. Rimer, P.G. Vekilov, Antimalarials inhibit hematin crystallization by unique drug-surface site interactions. Proceedings of the National Academy of Sciences of the USA 114, 7531-7536, 2017