Prof. Christopher Rowley

MoSE 3201A
Friday, August 18, 2017 - 11:00am to 12:00pm

The Right Method for the Right Problem: Modeling Ions, Membranes, and  Covalent-Modifiers

Our group develops new computational methods to study biophysical chemistry,  including topics like as membrane permeation, ion-biomolecule binding, and  the covalent modification of proteins. In this talk, I will present examples  of our recent work on these topics. The first topic is the permeation of  gasotransmitters through cell membranes. H2S, CO, and NO are endogenous signaling molecules with potential to be used as anti-inflammatory agents.  These molecules are able to permeate cell membranes rapidly without a  facilitator. Our simulations show that the small radii and hydrophobicity of these molecules allow them to diffuse freely through membranes, allowing them to react with intracellular targets rapidly [1]. Using a polarizable  force field and a model derived from the Generalized Langevin Equation, we  were able to predict the rate of permeability quantitatively. Our next  subject was the relative solubility of Mg(II) and Zn(II). QM/MM simulations  reveal that the greater Lewis acidity of Zn(II) results in its greater  solubility. Lastly, we have studied drugs that contain cysteine-targeting  electrophiles that form covalent bonds with their targets. A new class of  kinase-targeting anti-cancer drugs (e.g. ibrutinib) include an electrophilic  acrylamide group that reacts with an active site cysteine residue. By computationally screening hundreds of putative warheads, we found that  effective warheads must allow for slow and reversible additions, which  avoids non-selective modification of proteins. We have also developed a new  computational method to identify acidic cysteine residues that serve as  facile targets for covalent modification [3].

 [1] Riahi, S., Rowley C.N. Why Can Hydrogen Sulfide Permeate Cell Membranes?  J. Am. Chem. Soc. 2014, doi: 10.1021/ja508063s

[2] Riahi, S., Rowley C.N. J. Comput. Chem. 2014, doi: 10.1002/jcc.23716  [3] Awoonor-Williams, E., Rowley, C.N. J. Chem. Theory Comput., 2016, doi:  10.1021/acs.jctc.6b00631

Contact Information: 


Asst. Prof. Jesse G. McDaniel (

Map of Georgia Tech

School of Chemistry & Biochemistry

901 Atlantic Drive Atlanta, GA 30332-0400

(404) 894-4002 (phone) | (404) 894-7452 (fax)