2026-10-11T03:33:46Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33965701 2026-09-22T14:45:01Z category_1 category_4 category_13 category_14 category_15 category_16 category_19 category_21 category_46 category_931 category_135 portal_63 item_type_3 month_year_09_2026

Fragment OptimizationSimple SMILES String Manipulation Strategies to Optimize a Hit or Fragment Kevin P. Cusack (2365519) Jake M. Aquilina (12871972) Biophysics Biochemistry Genetics Molecular Biology Neuroscience Physiology Pharmacology Biotechnology Immunology Information Systems not elsewhere classified Computational Biology low data targets become important contributors source counterpart written alternative smiles patterns adme profiling prior smiles string alternative open type swaps systematically replaced silico </ several programs ring opening ring expansion proprietary licensing predictive modeling lead optimization knime workflow initially implemented generate atom fully open commercial solutions also provided AI/ML-based tools for generative and predictive modeling have become important contributors to small molecule drug discovery, enabling virtual compound design and ADME profiling prior to synthesis. Alongside these methods, simpler nonlearned strategies based on direct SMILES manipulation remain useful, particularly for low data targets. Herein is described a method for fragment optimization in which characters of a SMILES string are systematically replaced with alternative SMILES patterns to generate atom-type swaps, ring expansion/contraction, cyclization, ring opening, and fragment grafts. The method was initially implemented as a KNIME workflow and demonstrated on fragment-to-lead optimization of fragments from several programs. A fully open-source counterpart written in Python utilizing AutoDock Vina is also provided. Together, these tools are used in parallel with alternative open-source and commercial solutions to accelerate fragment-to-lead optimization through iterative <i>in silico</i> design and profiling, and require no AI/ML or proprietary licensing for the open source python version. 2026-09-22T00:00:00Z Dataset Dataset 10.1021/acsmedchemlett.6c00181.s002 https://figshare.com/articles/dataset/Fragment_Optimization_Simple_SMILES_String_Manipulation_Strategies_to_Optimize_a_Hit_or_Fragment/33965701 CC BY-NC 4.0