MOL2

MOL2 (Tripos MOL2, file extension .mol2 or .ml2) is a plain-text ASCII format developed by Tripos as the portable interchange representation of a molecule in its SYBYL molecular-modeling environment. Now maintained under Certara (which absorbed Tripos), it remains one of the most widely used formats in cheminformatics and structure-based drug design because, unlike the connection-table formats it competes with, it carries perceived chemistry — SYBYL atom types, bond orders, aromaticity, partial charges, and substructure/residue grouping — directly in the file rather than leaving it to be re-derived.

Structurally, a MOL2 file is free-format and divided into sections introduced by Record Type Indicators of the form @<TRIPOS>NAME. The core records are MOLECULE (name, atom/bond/substructure counts, a molecule type such as SMALL or PROTEIN, and a charge type such as GASTEIGER or NO_CHARGES), ATOM (per-atom id, name, x/y/z coordinates, SYBYL atom type, substructure id and name, and partial charge), and BOND (bond id, the two endpoint atom ids, and a bond type). Optional records include SUBSTRUCTURE, SET, and CRYSIN for crystallographic cell parameters. The distinctive SYBYL atom typing uses dotted labels — C.3, C.ar, N.am, O.2 — that encode hybridization, aromaticity, and chemical environment, and bond types are symbolic (1, 2, 3, am, ar, du). Multiple molecules or conformers are stored by simply concatenating blocks ("multi-mol2"), which makes it a common container for docking ligand libraries.

In the graph-data and format-conversion world, MOL2 is a molecular graph: atoms are nodes and bonds are typed edges. It sits alongside the MDL-derived Molfile and SDF as the standard 3D-coordinate carriers, complements the connectivity-only line notations SMILES and InChI, and is a routine target for the same toolchains — Open Babel, RDKit, and ChemDoodle all read and write it. Its main strengths are the explicit atom types, charges, and coordinates that docking and force-field workflows depend on.

Its chief weakness is inconsistency: the specification is loose and under-standardized, so files written by different programs (Open Babel, Corina, SYBYL) disagree on atom typing and charge conventions, and one tool frequently fails to parse another tool's MOL2 — a well-known interoperability hazard. It also lacks a rich metadata/property block, so pipelines needing tagged data often prefer SDF instead.