Local pair natural orbital coupled-cluster methods have seen much success recently, allowing for the application of “chemically accurate” approaches such as CCSD(T) to significantly larger systems. Notably, the DLPNO-CCSD(T) approach of Professor Frank Neese and coworkers has been utilized to run computations on whole proteins such as crambin (636 atoms) and insulin (789 atoms). At the CCSD(T) level of theory, local approximations have errors which are controllable to within 0.25 kcal/mol through tight parameters.

Precision bioconjugation techniques are essential for constructing well-defined protein-based therapeutics such as antibody-drug conjugates (ADCs). Among native amino acids, cysteine is particularly attractive for site-selective modification due to its high nucleophilicity and low natural abundance. However, most proteins contain multiple free cysteines, making it challenging to target specific residues without affecting protein structure or function.

Cell sorting enables the separation of specific cell types from heterogeneous populations and is widely used in biomedical research, drug development, and regenerative medicine. Existing methods fall into two categories: label-based techniques, such as fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS), which rely on antibodies conjugated to fluorescent dyes or magnetic beads; and label-free techniques, which exploit intrinsic physical properties such as size, deformability, or electrical charge.