Deciphering the biophysical aspects of the interaction of 3,5,4'-trihydroxy-trans-stilbene with ribonuclease A: spectroscopic and computational studies.

Drug-receptor interaction is an important aspect in drug action, drug discovery, and pharmacological aspects. The molecule 3,5,4'-trihydroxy-trans-stilbene known as resveratrol is a natural polyphenol and exhibits diverse biological activities. Ribonuclease A catalyses the degradation of RNA by its ribonucleolytic activity. The report presents the binding interaction of resveratrol with RNase A using experimental and theoretical techniques. Experimental studies revealed the interaction strength of 10 M order with a single binding site. Resveratrol quenched the ribonuclease A fluorescence with a quenching constant of 10 M range. The accessible fraction of the fluorophore was found to be 0.75 besides non-radiative energy transfer from ribonuclease A to resveratrol. The donor-acceptor distance was 2.14 nm from FRET calculations. No visible changes in the protein structure was evident from the circular dichroism studies. The interface residues involved in the interaction were obtained from docking studies. Further, the participation of the active site residues, His 12, His 119, and Lys 41 with interaction indicates the location of resveratrol near to the active site of ribonuclease A and indicates its possible potential to inhibit the ribonuclease A activity. The RMSD of less than 3 Å indicates stable conformation of protein in the complex. The protein RMSF value in the complex less than 3 Å shows no deviation of protein residues over time and thus suggests no conformational variation in the protein after binding.