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Updated: Nov 4, 2025

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
Published on: January 26, 2024
Side-Chain Polarity Modulates the Intrinsic Conformational Landscape of Model Dipeptides
Debayan Chakraborty1, Atreyee Banerjee2,3, David J Wales2
1Department of Chemistry, The University of Texas at Austin, 24th Street Stop A5300, Austin, Texas 78712, United States.
Abstract:
The intrinsic conformational preferences of small peptides may provide additional insight into the thermodynamics and kinetics of protein folding. In this study, we explore the underlying energy landscapes of two model peptides, namely, Ac-Ala-NH2 and Ac-Ser-NH2, using geometry-optimization-based tools developed within the context of energy landscape theory. We analyze not only how side-chain polarity influences the structural preferences of the dipeptides, but also other emergent properties of the landscape, including heat capacity profiles, and kinetics of conformational rearrangements. The contrasting topographies of the free energy landscape agree with recent results from Fourier transform microwave spectroscopy experiments, where Ac-Ala-NH2 was found to exist as a mixture of two conformers, while Ac-Ser-NH2 remained structurally locked, despite exhibiting an apparently rich conformational landscape.
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