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Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field. In this report, industry members of the consortium worked together to objectively evaluate the performance of the force fields (referred to here as OpenFF) produced by the initiative on a combined public and proprietary dataset of 19,653 relevant molecules selected from their internal research and compound collections. This evaluation was important because it was completely blind; at most partners, none of the molecules or data were used in force field development or testing prior to this work. We compare the Open Force Field "Sage" version 2.0.0 and "Parsley" version 1.3.0 with GAFF-2.11-AM1BCC, OPLS4, and SMIRNOFF99Frosst. We analyzed force-field-optimized geometries and conformer energies compared to reference quantum mechanical data. We show that OPLS4 performs best, and the latest Open Force Field release shows a clear improvement compared to its predecessors. The performance of established force fields such as GAFF-2.11 was generally worse. While OpenFF researchers were involved in building the benchmarking infrastructure used in this work, benchmarking was done entirely in-house within industrial organizations and the resulting assessment is reported here. This work assesses the force field performance using separate benchmarking steps, external datasets, and involving external research groups. This effort may also be unique in terms of the number of different industrial partners involved, with 10 different companies participating in the benchmark efforts.

Background: One-step cell-based techniques of cartilage repair that lead to restoration of durable chondral tissue and long-term maintenance of joint function are cost-effective and ideal for routine use. Purposes: To examine the long-term clinical outcomes, after a mean follow-up duration of 14 years, of cartilage repair in the knee using a hyaluronic acid–based scaffold in association with bone marrow aspirate concentrate (HA-BMAC) and to evaluate the effect of age, lesion characteristics, and associated treatments on the outcome of this cartilage repair method. Study Design: Case series; Level of evidence, 4. Methods: Patients were followed prospectively for a mean duration of 14.0 years after undergoing treatment of knee full-thickness articular cartilage injury using HA-BMAC. Clinical evaluation consisted of the patient-reported scoring tools of the visual analog scale and the Knee injury and Osteoarthritis Outcome Score, which were completed preoperatively and at the time of final follow-up. Results: A total of 26 patients with a mean age of 48.3 years (17 male, 9 female) and median chondral lesion size of 6.6 cm2 (range, 1-27 cm2) were followed prospectively. There were 3 treatment failures, and 1 patient who underwent medial compartment unicompartmental arthroplasty 12 years after HA-BMAC treatment of patellar chondral injury. Of the 22 remaining patients, after a mean final follow-up duration of 14.0 years (range, 12-16 years), the median visual analog scale score of 0.6 was significantly decreased from the preoperative median score of 5.0 (P <.001). The median Knee injury and Osteoarthritis Outcome Score Pain (92), Symptoms (86), Activities of Daily Living (96), Sports (85), and Quality of Life (88) subscale values were all increased compared with the preoperative scores (P ≤.001). There was no correlation of clinical outcome score and body mass index. Conclusion: One-step cartilage repair of full-thickness chondral defects in the knee using an HA-BMAC led to successful long-term clinical outcomes and maintenance of joint junction after a mean follow-up duration of 14 years. Long-term clinical success in active, nonobese patients has been uniformly demonstrated across a wide range of patient ages and lesion types, including cases of multicompartment involvement, treatment of associated conditions, and large or bipolar chondral lesions. [ABSTRACT FROM AUTHOR]