Our understanding of the “long range” electrodynamic, electrostatic, and polar interactions that dominate the organization of small objects at separations beyond an interatomic bond length is reviewed. From this basic-forces perspective, a large number of systems are described from which one can learn about these organizing forces and how to modulate them. The many practical systems that harness these nanoscale forces are then surveyed. The survey reveals not only the promise of new devices and materials, but also the possibility of designing them more effectively.

We have studied some consequences of a generalized theory of electrostatic interactions between two macroscopic surfaces immersed in a dilute electrolyte. The ionic interactions close to the two bounding surfaces were supposed to be specifically affected by the presence of the surfaces, leading to a surface contribution to the total free energy density of the system. A functional integral (sine-Gordon) representation of the grand canonical partition function was derived and evaluated in the saddle-point approximation, leading to the repulsive mean-field and an attractive first-order correlation correction to the interaction free energy. The magnitude of the correlation term was investigated in detail and general conditions on the form of the surface-specific free energy density were derived that would lead to an anomalously large exponentially decaying attractive interactions. We present some arguments in favor of the view that this anomalous long-range attraction could well represent a case for the electrostatic nature of the recently measured long-range ‘‘hydrophobic’’ attraction.

We summarize some aspects of electrostatic interactions in the context of viruses. A simplified but, within well defined limitations, reliable approach is used to derive expressions for electrostatic energies and the corresponding osmotic pressures in single-stranded RNA viruses and double-stranded DNA bacteriophages. The two types of viruses differ crucially in the spatial distribution of their genome charge which leads to essential differences in their free energies, depending on the capsid size and total charge in a quite different fashion. Differences in the free energies are trailed by the corresponding characteristics and variations in the osmotic pressure between the inside of the virus and the external bathing solution.

The spike protein of SARS-CoV-2 binds to the ACE2 receptor via its receptor-binding domain (RBD), with the RBD–ACE2 complex presenting an essential molecular target for vaccine development to stall the virus infection proliferation. The computational analyses at molecular, amino acid (AA), and atomic levels have been performed systematically to identify the key interacting AAs in the formation of the RBD–ACE2 complex for SARS-CoV and SARS-CoV-2 with its Alpha and Beta variants. Our study uses the molecular dynamics (MD) simulations with the molecular mechanics generalized Born surface area (MM-GBSA) method to predict the binding free energy (BFE) and to determine the actual interacting AAs, as well as two ab initio quantum chemical protocols based on the density functional theory (DFT) implementation. Based on MD results, Q⁴⁹³, Y⁵⁰⁵, Q⁴⁹⁸, N⁵⁰¹, T⁵⁰⁰, N⁴⁸⁷, Y⁴⁴⁹, F⁴⁸⁶, K⁴¹⁷, Y⁴⁸⁹, F⁴⁵⁶, Y⁴⁹⁵, and L⁴⁵⁵ have been identified as hotspots in SARS-CoV-2 RBD, while those in ACE2 are K³⁵³, K³¹, D³⁰, D³⁵⁵, H³⁴, D³⁸, Q²⁴, T²⁷, Y⁸³, Y⁴¹, and E³⁵. RBD with Alpha and Beta variants has slightly different interacting AAs due to N501Y mutation. Both the electrostatic and hydrophobic interactions are the main driving force to form the AA–AA binding pairs. We confirm that Q⁴⁹³, Q⁴⁹⁸, N⁵⁰¹, F⁴⁸⁶, K⁴¹⁷, and F⁴⁵⁶ in RBD are the key residues responsible for the tight binding of SARS-CoV-2 with ACE2 compared to SARS-CoV. RBD with the Alpha variant binds with ACE2 stronger than the wild-type RBD or Beta. In the Beta variant, K417N reduces the binding, E484K slightly enhances it, and N501Y significantly increases it as in Alpha. The DFT results reveal that N⁴⁸⁷, Q⁴⁹³, Y⁴⁴⁹, T⁵⁰⁰, G⁴⁹⁶, G⁴⁴⁶, and G⁵⁰² in RBD of SARS2 form pairs via specific hydrogen bonding with Q²⁴, H³⁴, E³⁵, D³⁸, Y⁴¹, Q⁴², and K³⁵³ in ACE2.