PDBsum entry 5ede

Hydrolase

PDB id: 5ede

Contents

Protein chains

314 a.a.

Ligands

GOL ×2

5M6 ×4

Metals

_ZN ×4

_MG ×4

Waters ×780

References listed in PDB file

Key reference

• Title: A real-World perspective on molecular design.
• Authors: B.Kuhn, W.Guba, J.Hert, D.Banner, C.Bissantz, S.Ceccarelli, W.Haap, M.Körner, A.Kuglstatter, C.Lerner, P.Mattei, W.Neidhart, E.Pinard, M.G.Rudolph, T.Schulz-Gasch, T.Woltering, M.Stahl.
• Ref.: J Med Chem, 2016, 59, 4087-4102. [DOI no: 10.1021/acs.jmedchem.5b01875]
• PubMed id: 26878596

Abstract

We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction.