Accounting for receptor flexibility and enhanced sampling methods in computer aided drug design
By W. Sinko, Steffen Lindert, James Andrew McCammon. 2013
116 citations recorded by the source corpus.
Protein flexibility plays a major role in biomolecular recognition. In many cases, it is not obvious how molecular structure will change upon association with other molecules. In proteins, these changes can be major, with large deviations in overall backbone structure, or they can be more subtle as in a side‐chain rotation. Either way the algorithms that predict the favorability of biomolecular association require relatively accurate predictions of the bound structure to give an accurate assessment of the energy involved in association. Here, we review a number of techniques that have been proposed to accommodate receptor flexibility in the simulation of small molecules binding to protein receptors. We investigate modifications to standard rigid receptor docking algorithms and also explore enhanced sampling techniques, and the combination of free energy calculations and enhanced sampling techniques. The understanding and allowance for receptor flexibility are helping to make computer simulations of ligand protein binding more accurate. These developments may help improve the efficiency of drug discovery and development. Efficiency will be essential as we begin to see personalized medicine tailored to individual patients, which means specific drugs are needed for each patient’s genetic makeup.
Subfields: Computational Theory and Mathematics, Molecular Biology, Radiology, Nuclear Medicine and Imaging
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Computational Theory and Mathematics
- Sandeepkumar Kothiwale
- Jens Meiler
- E. W. Lowe
- Anima Anandkumar
- Weili Nie
- Arash Vahdat
- Gregory Sliwoski
- Thomas F. Miller
In Molecular Biology
- Sandeepkumar Kothiwale
- Jens Meiler
- E. W. Lowe
- Anima Anandkumar
- Weili Nie
- Arash Vahdat
- Gregory Sliwoski
- Thomas F. Miller
In Radiology, Nuclear Medicine and Imaging
Citations in the corpus
- Computational Methods in Drug Discovery (2014, methodology): “Conformational variability is seen in unbound form and different apo structures (B-Rao et al., 2009; Sinko et al., 2013).”
- Dynamic-Backbone Protein-Ligand Structure Prediction with Multiscale Generative Diffusion Models (2022, background): “[13] William Sinko, Steffen Lindert, and J Andrew McCammon.”