The Xplor-NIH NMR molecular structure determination package is a software tool developed at the National Institutes of Health (NIH) for determining the three-dimensional structures of biomolecules using NMR spectroscopy. It is based on the original XPLOR program, with additional NMR-specific features and a new C++ framework for enhanced flexibility and performance. The package includes a variety of energy terms for NMR structure determination, such as covalent geometry, non-bonded contacts, and NMR observables like NOE (Nuclear Overhauser Effect) restraints. It also incorporates knowledge-based potentials of mean force derived from high-resolution structures in the PDB database to improve conformational sampling during simulations. The Xplor-NIH package supports both Cartesian and torsion angle coordinates for molecular dynamics and minimization, and includes a reduced variable dynamics module for efficient optimization. It provides interfaces with Python and TCL scripting languages, enabling the development of new potential energy terms and optimization methods. The package also includes a direct interface to the VMD-XPLOR visualization package for structure analysis and visualization. Xplor-NIH is distributed with a comprehensive set of regression tests to ensure its reliability and correctness. It is available for non-commercial use from the URL http://nmr.cit.nih.gov/xplor-nih/, and commercial use requires licensing from Accelrys Corporation. The package supports multiple hardware and operating system platforms, and includes example scripts, supporting databases, and test suites for ease of use. The software is designed to be flexible and efficient, with a focus on accurate and reliable NMR structure determination.The Xplor-NIH NMR molecular structure determination package is a software tool developed at the National Institutes of Health (NIH) for determining the three-dimensional structures of biomolecules using NMR spectroscopy. It is based on the original XPLOR program, with additional NMR-specific features and a new C++ framework for enhanced flexibility and performance. The package includes a variety of energy terms for NMR structure determination, such as covalent geometry, non-bonded contacts, and NMR observables like NOE (Nuclear Overhauser Effect) restraints. It also incorporates knowledge-based potentials of mean force derived from high-resolution structures in the PDB database to improve conformational sampling during simulations. The Xplor-NIH package supports both Cartesian and torsion angle coordinates for molecular dynamics and minimization, and includes a reduced variable dynamics module for efficient optimization. It provides interfaces with Python and TCL scripting languages, enabling the development of new potential energy terms and optimization methods. The package also includes a direct interface to the VMD-XPLOR visualization package for structure analysis and visualization. Xplor-NIH is distributed with a comprehensive set of regression tests to ensure its reliability and correctness. It is available for non-commercial use from the URL http://nmr.cit.nih.gov/xplor-nih/, and commercial use requires licensing from Accelrys Corporation. The package supports multiple hardware and operating system platforms, and includes example scripts, supporting databases, and test suites for ease of use. The software is designed to be flexible and efficient, with a focus on accurate and reliable NMR structure determination.