Published Research

We have provided a demonstration of how to use QM-based X-ray refinement to inform the often difficult choice about where to put a proton. This seemingly simple atom has given practioners in the field a lot of grief over the years, and it turns out that QM-based methods do a really good job of helping you make this important decision!

The recognition and association of donepezil with acetylcholinesterase (AChE) has been extensively studied in the past several decades because of the former’s use as a palliative treatment for mild Alzheimer disease. Herein, we examine the conformational properties of donepezil and we re-examine the donepezil-AChE crystal structure using combined quantum mechanical/molecular mechanical (QM/MM) X-ray refinement tools.....

The conformational profiles of unbound all-trans and 9-cis retinoic acid (RA) have been determined using classical and quantum mechanical calculations. Sixty-six all-trans-RA (ATRA) and 48 9-cis-RA energy minimum conformers were identified via HF/6-31G* geometry optimizations in vacuo. Their relative conformational energies were estimated utilizing the M06, M06-2x, and MP2 methods combined with the 6-311+G(d,p), aug-cc-pVDZ, and aug-cc-pVTZ basis sets, as well as complete basis set MP2 extrapolations using the latter two basis sets....

Retinoic acid (RA) is a vitamin A derivative, which modifies the appearance of fine wrinkles and roughness of facial skin and treats acne and activates gene transcription by binding to heterodimers of the retinoic acid receptor (RAR) and the retinoic X receptor (RXR). There are series of protein bound RA complexes available in the protein databank (PDB), which provides a broad range of information about the different bioactive conformations of RA....

An ongoing question regarding the energetics of protein-ligand binding has been; what is the strain energy that a ligand pays (if any) when binding to its protein target? The traditional method to estimate strain energy uses force fields to calculate the energy difference between the ligand bound conformation and its nearest local minimum/global minimum on the gas-phase or aqueous phase potential energy surface....