Regioselectivity models are of key importance to the implementation of C–H functionalisations in synthetic route planning. In structure- and fragment-based drug discovery (SBDD/FBDD), ligand-target affinity is enhanced by elaborating weak hits into potent ...

Recently several co-folding AI are available, for example AF3, Chai-1, protenix and openfold. This area is hot and growing day by day. Co-Folding AI has potential for taking SBDD approach without determining the target protein-ligand structure. As most of readers know that there are still limitation of using co-folding AI for SBDD but really useful I think. I have an interest in openfold because openfold disclose code and has good open scientific community.

Conformational strain, the energy a ligand pays to adopt its bound conformation, contributes to binding affinity but is routinely misestimated. The standard estimate references a single gasphase energ...

Generative structure-based drug design (SBDD) models have shown great promise for accelerating our ability to discover novel drug candidates. However, these models have been criticized for producing c...

How to make use of one-click, automated data processing workflows that can provide equal or better results as manual processing

Cryo-EM revealed the molecular basis of KOR signaling bias, enabling structure-based drug design of an anti-pruritic peptide with reduced side effects.

Targeted Protein Degrader (TPD) is one of the attractive modality of recent drug discovery area. As most of readers know that First TPD, ER degrader gains FDA approval in this year. TPD molecule induce PPI of POI and E3 ligase and degradation of POI. It is unique mechanism because chemical compounds can induce artificial degradation process. But the process is really complex so it's difficult to design TPD molecule rationally such as SBDD.

Understanding protein-ligand interaction is important for rational drug design. We can use X-ray co crystal structures for SBDD and information of ligand binding site is essential reagion. For example QM/MM approach applies QM level calculation to around binding site and applies MM to far from binding site. QM often offer more accurate energy state but its computational cost is high. So MM is used for not critical reagion for protein-ligand binding.