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A next‐generation protocol (Poltype 2) has been developed which automatically generates AMOEBA polarizable force field parameters for small molecules. Both features and computational efficiency have been drastically improved. Notable advances include improved database transferability using SMILES, robust torsion fitting, non‐aromatic ring torsion parameterization, coupled torsion‐torsion parameterization, Van der Waals parameter refinement using ab initio dimer data and an intelligent fragmentation scheme that produces parameters with dramatically reduced ab initio computational cost. Additional improvements include better local frame assignment for atomic multipoles, automated formal charge assignment, Zwitterion detection, smart memory resource defaults, parallelized fragment job submission, incorporation of Psi4 quantum package, ab initio error handling, ionization state enumeration, hydration free energy prediction and binding free energy prediction. For validation, we have applied Poltype 2 to ~1000 FDA approved drug molecules from DrugBank. The ab initio molecular dipole moments and electrostatic potential values were compared with Poltype 2 derived AMOEBA counterparts. Parameters were further substantiated by calculating hydration free energy (HFE) on 40 small organic molecules and were compared with experimental data, resulting in an RMSE error of 0.59 kcal/mol. The torsion database has expanded to include 3543 fragments derived from FDA approved drugs. Poltype 2 provides a convenient utility for applications including binding free energy prediction for computational drug discovery. Further improvement will focus on automated parameter refinement by experimental liquid properties, expansion of the Van der Waals parameter database and automated parametrization of modified bio‐fragments such as amino and nucleic acids.

 

Cerebral aneurysm clips are biomedical implants applied by neurosurgeons to re-approximate arterial vessel walls and prevent catastrophic aneurysmal hemorrhages in patients. Current methods of aneurysm clip production are labor intensive and time-consuming, leading to high costs per implant and limited variability in clip morphology. Metal additive manufacturing is investigated as an alternative to traditional manufacturing methods that may enable production of patient-specific aneurysm clips to account for variations in individual vascular anatomy and possibly reduce surgical complication risks. Relevant challenges to metal additive manufacturing are investigated for biomedical implants, including material choice, design limitations, postprocessing, printed material properties, and combined production methods. Initial experiments with additive manufacturing of 316 L stainless steel aneurysm clips are carried out on a selective laser melting (SLM) system. The dimensions of the printed clips were found to be within 0.5% of the dimensions of the designed clips. Hardness and density of the printed clips (213 ± 7 HV1 and 7.9 g/cc, respectively) were very close to reported values for 316 L stainless steel, as expected. No ferrite and minimal porosity is observed in a cross section of a printed clip, with some anisotropy in the grain orientation. A clamping force of approximately 1 N is measured with a clip separation of 1.5 mm. Metal additive manufacturing shows promise for use in the creation of custom aneurysm clips, but some of the challenges discussed will need to be addressed before clinical use is possible.