Increasing atmospheric CO2 measurements in North America, especially in urban areas, may help enable the development of an operational CO2 emission monitoring system. However, isolating the fossil fuel emission signal in the atmosphere requires factoring out CO2 fluctuations due to the biosphere, especially during the growing season. To help improve simulations of the biosphere, here we customize the Vegetation Photosynthesis and Respiration Model (VPRM) at high-resolution for an eastern North American domain, upwind of coastal cities from Washington D.C. to Boston, MA, optimizing parameters using domain-specific flux tower data from 2001 to the present. We run three versions of VPRM from November 2016 to October 2017 using i) annual (VPRMann) and ii) seasonal parameters (VPRMseas), and then iii) modifying the respiration equation to include the Enhanced Vegetation Index (EVI), a squared temperature term and interactions between temperature and water stress (VPRMnew). VPRM flux estimates are evaluated by comparison with other models (the Carnegie-Ames-Stanford Approach model, or CASA, and the Simple Biosphere Model v4), and with comparison to atmospheric CO2 mole fraction data at 21 surface towers. Results show that VPRMnew is relatively unbiased and outperforms all other models in explaining CO2 variability from April to October, while VPRMann overestimates growing season sinks by underestimating summertime respiration. Despite unknown remaining errors in VPRMnew, and uncertainties associated with other components of the atmospheric CO2 comparisons, VPRMnew appears to hold promise for more effectively separating anthropogenic and biospheric signals in atmospheric inversion systems in eastern North America.