Honors & Awards

  • Graduate Research Award in Chemistry, University of Southern California (2010, 2013)
  • WiSE Travel Grant for Graduate Students and Post-doctoral Fellows, University of Southern California (2010, 2012)
  • Department of Chemistry Predoctoral Scholarship, University of Southern California (2009-13)
  • Academician R.V. Khokhlov competition award, Lomonosov Moscow State University (2005)
  • Diploma with honors, Lomonosov Moscow State University (2005)
  • Gold Medal, Lomonosov Moscow State University (2005)
  • President’s scholarship, Lomonosov Moscow State University (2004-05)
  • The “Garant” company scholarship, Lomonosov Moscow State University (2004-05)
  • Kurchatov’s scholarship, Lomonosov Moscow State University (2003-04)
  • Higher scholarship, Lomonosov Moscow State University (2000-05)

Boards, Advisory Committees, Professional Organizations

  • Member, American Society of Human Genetics (2013 - 2014)
  • Member, Biophysical Society (2010 - Present)
  • Member, American Chemical Society (2011 - 2012)
  • Member, Protein Society (2010 - 2011)
  • Member, Interdisciplinary Program in Drug Design, USC (2009 - 2013)

Professional Education

  • Doctor of Phylosophy, University of Southern California, Computational Chemistry (2013)
  • Master of Science, Lomonosov Moscow State University, Physics/Biophysics (2005)

Stanford Advisors

Research & Scholarship

Current Research and Scholarly Interests

I have always been passionate about biology and curious about the physical mechanisms that underlie biological functions. I received an MS in Biophysics from the Physics Department of Moscow State University, and then a PhD in Computational Chemistry from the Chemistry Department of the University of Southern California. With my background in physics and experience in protein simulations I have decided to switch into the field of human genetics, as I am very excited about its application to human health and personalized medicine. I joined the group of Carlos Bustamante in September 2013 and am currently working on the Clinical Genome project, where I am trying to improve methods for variant assessment using information about protein structure.

Lab Affiliations


Journal Articles

  • On the Nature of the Apparent Free Energy of Inserting Amino Acids into Membrane through the Translocon. journal of physical chemistry. B Rychkova, A., Warshel, A. 2013; 117 (44): 13748-13754


    The nature of the biological free energy scale (ΔGapp), obtained from translocon mediated insertion studies, has been a major puzzle and the subject of major controversies. Part of the problem has been the complexity of the insertion process that discouraged workers from considering the feasible kinetics schemes and left the possible impression that ΔGapp presents some simple partition. Here we extend and clarify our recent analysis of the insertion problem using well-defined kinetics schemes and a free energy profile. We point out that although the rate constants of some steps are far from being obvious, it is essential to consider explicitly such schemes in order to advance in analyzing the meaning of ΔGapp. It is then shown that under some equilibrium conditions the kinetics scheme leads to a simple formula that allows one to relate ΔGapp to the actual free energy of partitioning between the water, the membrane, and the translocon. Other options are also considered (including limits with irreversible transitions that can be described by linear free energy relationships (LFERs)). It is concluded that it is unlikely that a kinetics plus thermodynamic based analysis can lead to a result that identifies ΔGapp with the partition between the membrane and the translocon. Thus, we argue that unless such analysis is presented, it is unjustified to assume that ΔGapp corresponds to the membrane translocon equilibrium or to some other arbitrary definition. Furthermore, we point out that the presumption that it is sufficient to just calculate the PMF for going from the translocon (TR) to the membrane and then to assume irreversible diffusive motion to water and for further entrance to the membrane is not a valid analysis. Overall, we point out that it is important to try to relate ΔGapp to a well-defined kinetics scheme (regardless of the complication of the system) in order to determine whether the energies of inserting positively charged residues to the membrane are related to the corresponding ΔGapp. It is also suggested that deviations from our simple formula for equilibrium conditions can help in identifying and analyzing kinetics barriers.

    View details for DOI 10.1021/jp406925y

    View details for PubMedID 24087983

  • Simulating the pulling of stalled elongated peptide from the ribosome by the translocon PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rychkova, A., Mukherjee, S., Bora, R. P., Warshel, A. 2013; 110 (25): 10195-10200


    The nature of the coupling between the stalling of the elongated nascent peptide chain in the ribosome and its insertion through the translocon is analyzed, focusing on the recently discovered biphasic force that overcomes the stalling barrier. The origin of this long-range coupling is explored by coarse-grained simulations that combine the translocon (TR) insertion profile and the effective chemical barrier for the extension of the nascent chain in the ribosome. Our simulation determined that the inserted H segment is unlikely to climb the TR barrier in parallel with the peptide synthesis chemical step and that the nascent chain should first overcome the chemical barriers and move into the ribosome-TR gap region before the insertion into the TR tunnel. Furthermore, the simulations indicate that the coupled TR-chemistry free energy profile accounts for the biphasic force. Apparently, although the overall elongation/insertion process can be depicted as a tug-of-war between the forces of the TR and the ribosome, it is actually a reflection of the combined free-energy landscape. Most importantly, the present study helps to relate the experimental observation of the biphasic force to crucial information about the elusive path and barriers of the TR insertion process.

    View details for DOI 10.1073/pnas.1307869110

    View details for Web of Science ID 000321500200044

    View details for PubMedID 23729811

  • Exploring the nature of the translocon-assisted protein insertion PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rychkova, A., Warshel, A. 2013; 110 (2): 495-500


    The elucidation of the molecular nature of the translocon-assisted protein insertion is a challenging problem due to the complexity of this process. Furthermore, the limited availability of crucial structural information makes it hard to interpret the hints about the insertion mechanism provided by biochemical studies. At present, it is not practical to explore the insertion process by brute force simulation approaches due to the extremely lengthy process and very complex landscape. Thus, this work uses our previously developed coarse-grained model and explores the energetics of the membrane insertion and translocation paths. The trend in the calculated free-energy profiles is verified by evaluating the correlation between the calculated and observed effect of mutations as well as the effect of inverting the signal peptide that reflects the "positive-inside" rule. Furthermore, the effect of the tentative opening induced by the ribosome is found to reduce the kinetic barrier. Significantly, the trend of the forward and backward energy barriers provides a powerful way to analyze key energetics information. Thus, it is concluded that the insertion process is most likely a nonequilibrium process. Moreover, we provided a general formulation for the analysis of the elusive apparent membrane insertion energy, ΔG(app), and conclude that this important parameter is unlikely to correspond to the free-energy difference between the translocon and membrane. Our formulation seems to resolve the controversy about ΔG(app) for Arg.

    View details for DOI 10.1073/pnas.1220361110

    View details for Web of Science ID 000313906600030

    View details for PubMedID 23269832

  • On the energetics of translocon-assisted insertion of charged transmembrane helices into membranes PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Rychkova, A., Vicatos, S., Warshel, A. 2010; 107 (41): 17598-17603


    The understanding of the mechanism of insertion of transmembrane (TM) helixes through the translocon presents a major open challenge. Although the experimental information about the partition of the inserted helices between the membrane and the solution contains crucial information about this process, it is not clear how to extract this information. In particular, it is not clear how to rationalize the small apparent insertion energy, ΔG(app), of an ionized residue in the center of a TM helix. Here we explore the nature of the insertion energies, asking what should be the value of these parameters if their measurements represent equilibrium conditions. This is done using a coarse-grained model with advanced electrostatic treatment. Estimating the energetics of ionized arginine of a TM helix in the presence of neighboring helixes or the translocon provides a rationale for the observed ΔG(app) of ionized residues. It is concluded that the apparent insertion free energy of TM with charged residues reflects probably more than just the free energy of moving the isolate single helix from water into the membrane. The present approach should be effective not only in exploring the mechanism of the operation of the translocon but also for studies of other membrane proteins.

    View details for DOI 10.1073/pnas.1012207107

    View details for Web of Science ID 000282809700030

    View details for PubMedID 20876127

  • The strength of transcription-factor binding modulates co-variation in transcriptional networks TRENDS IN GENETICS Nuzhdin, S. V., Rychkova, A., Hahn, M. W. 2010; 26 (2): 51-53


    An appreciable fraction of the transcriptome differs in level of expression among individuals. Transcription factor (TF) expression and DNA binding causes cell-specific activation and repression of downstream targets, and TF expression levels vary across individuals. However, it is not clear how the strength of DNA binding for individual TFs translates into regulatory control, or whether a different set of binding motifs is used for strongly regulated modules. Here we integrate two publicly available data sets in Drosophila melanogaster, as well as conduct novel analyses, to address these questions.

    View details for DOI 10.1016/j.tig.2009.12.005

    View details for Web of Science ID 000274987400002

    View details for PubMedID 20080313

  • Computational Approach to Study Membrane Protein Topology BIOPHYSICAL JOURNAL Rychkova, A., Warshel, A. 2012; 102 (3): 624A-624A
  • Membrane protein insertion and translocation studied by computational approach ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY Rychkova, A., Warshel, A. 2011; 241
  • Computational Studies of Translocon-Assisted Processes of Membrane Protein Insertion and Translocation BIOPHYSICAL JOURNAL Rychkova, A., Warshel, A. 2011; 100 (3): 544-544
  • The Effect of a Hydration Pocket on the Function Of nAChR Studied by Computational Approach BIOPHYSICAL JOURNAL Rychkova, A. 2010; 98 (3): 133A-133A
  • A new approach to the problem of oxygen formation in photosynthesis BIOFIZIKA Denisenko, A. S., Kukushkin, A. K. 2005; 50 (5): 833-842


    A detailed quantum-mechanical analysis of the model of water oxidizing complex, based on recent X-ray data on the structure of PSII, was made. A mechanism of water oxidation was suggested and explained for the first time. The role of three manganese atoms that are not involved directly in water oxidation, the role of the cubic structure of the complex, and the necessity of the presence of calcium and chlorine atoms during water oxidation are discussed. Theoretical computations of the energies of the complex in each S-state were made.

    View details for Web of Science ID 000232626000010

    View details for PubMedID 16248158

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